During the study period, a total of 48 692 patients were treated with various antibiotics, with samples taken from 27 792 (57.1%) patients within 2 days before or after starting antibiotic treatment. Among them, 19 868 (71.5%) of patient samples were taken before antibiotic therapy (SBA group), and 7 924 (28.5%) of patient samples were taken after antibiotic therapy (SAA group).
Patient characteristics and culture positive rate
The demographic characteristics of the included patients are shown in Table 1. Patients in the SAA group were older than those in the SBA group ( P<0.001). And both groups had a male predominance (62.8% in the SBA group and 62.3% in the SAA group; P = 0.443). Compared with the SAA group, the SBA group included more patients from ICU and internal departments(both P<0.001), with less subjects from surgery departments and other departments (both P<0.001), indicating patients from the latter departments were more likely to be exposed to antibiotics before clinical specimens collected.
The microbiological results suggested that the culture positive rate in the SBA group was higher than that of the SAA group (28.4% vs. 25.4%; P<0.001), but there was no significant difference in the proportion of polymicrobial results between the two groups (15.3% in the SBA group vs. 15.9% in the SAA group; P = 0.525).
Table 1 Characteristics, clinical specimen distribution, and culture positive rate of SBA and SAA groups
|
SBA group
N=19 868
|
SAA group
N=7 924
|
P value
|
Demographic
|
|
|
|
Age in yr, medians (IQR)
|
60 (47-70)
|
61(49-72)
|
<0.001
|
male (%)
|
12 477 (62.8%)
|
4 938 (62.3%)
|
0.443
|
Department distribution
|
|
|
|
Intensive Care Unit
|
1 582 (8.0%)
|
499 (6.3%)
|
<0.001
|
Surgery departments
|
8 760 (44.1%)
|
3 873 (48.9%)
|
<0.001
|
Internal departments
|
8 849 (44.5%)
|
3 114 (39.3%)
|
<0.001
|
Others
|
677 (3.4%)
|
428 (5.5%)
|
<0.001
|
Distribution of Clinical specimens
|
|
|
|
Respiratory specimens a
|
7 351 (37.0%)
|
3 162 (39.9%)
|
<0.001
|
Blood
|
4 229 (21.3%)
|
1 196 (15.1%)
|
<0.001
|
Body fluid specimens b
|
1 495 (7.5%)
|
1 131 (14.3%)
|
<0.001
|
Urine
|
4 311 (21.7%)
|
947 (12.0%)
|
<0.001
|
Stool
|
403 (2.0%)
|
297 (3.7%)
|
<0.001
|
Other specimens c
|
2 079 (10.5%)
|
1 191 (15.0%)
|
<0.001
|
Culture positive rate
|
|
|
|
Culture positive, n (%)
|
5 650 (28.4%)
|
2 014 (25.4%)
|
<0.001
|
Polymicrobial result, n (%)d
|
864 (15.3%)
|
320 (15.9%)
|
0.525
|
Abbreviations: SBA, specimen taken before antibiotic therapy; SAA, specimen taken after antibiotic therapy.
a including sputum, throat swab, tracheal aspirate, protected bronchial brush, and bronchoalveolar lavage
b including cerebrospinal fluid, pleural fluid, ascites, bile, puncture fluid, and pericardial effusion
c including intravascular catheter tip, various secretions, peritoneal dialysate, pus, drainage fluid, biopsy tissue and other specimens.
d Polymicrobial result was defined as more than one pathogen cultured from the same specimen.
Antimicrobial used in SAA groups
We classified antimicrobial drugs (either intravenously or orally) prescribed before sampling in SAA group, as shown in Fig.1. The common antibiotics used in SAA group were Cephalosporins (32.3%), β-lactamase inhibitor complex (31.3%),Carbapenems (18.7%), and Quinolones (10.2%).
Clinical specimen distribution
There was a significant difference in clinical specimen distribution between the two groups as shown in Table 1. The proportion of blood and urine specimens taken from the SBA group was higher than that of the SAA group (21.3% vs. 15.1% and 21.7% vs. 12.0%, respectively, both P<0.001), while the proportion of respiratory secretions (including sputum, throat swab, tracheal aspirate, protected bronchial brush, and bronchoalveolar lavage), body fluid specimens (including cerebrospinal fluid, pleural fluid, ascites, bile, puncture fluid, and pericardial effusion), stool, and other specimens (including intravascular catheter tip, various secretions, peritoneal dialysate, pus, drainage fluid, biopsy tissue and other specimens) sampled from the SBA group were lower than those of the SAA group with significance (37.0% vs. 39.9%, 7.5% vs. 14.3%, 2.0% vs. 3.7%, 10.5% vs. 15.0%, respectively, all P<0.001).
Microbial distribution isolated from specimens
Final culture results were made available by aCDSS, which yielded a total of 8 850 isolates, with 6 516 strains isolated from the SBA group and 2 334 from the SAA group. Differences in microbial distribution between the two groups are shown in Table 2.
Table 2 Distribution of microorganisms isolated from specimens taken from SBA and SAA groups
organisms
|
|
No. of Isolates in SBA Group
(N=6 516), n (%)
|
No. of Isolates in SAA Group
(N=2 334), n (%)
|
P value
|
Bacteria
|
|
|
6 256 (96.0%)
|
2 138 (91.6%)
|
<0.001
|
|
Gram-positive organism
|
|
1 773 (27.2%)
|
577 (24.7%)
|
0.020
|
|
|
S. aureus
|
556 (8.5%)
|
232 (9.9%)
|
0.041
|
|
|
CNS
|
469 (7.2%)
|
105 (4.5%)
|
<0.001
|
|
|
Streptococcus spp.
|
311 (4.8%)
|
64 (2.7%)
|
<0.001
|
|
|
Enterococcus spp.
|
437 (6.7%)
|
176 (7.5%)
|
0.173
|
|
Gram-negative organism
|
|
4 268 (65.5%)
|
1 515 (64.9%)
|
0.607
|
|
|
Enterobacteriaceae
|
2 777 (42.6%)
|
847 (36.3%)
|
<0.001
|
|
|
E. coli
|
1 008 (15.5%)
|
226 (9.7%)
|
<0.001
|
|
|
K. pneumoniae
|
1 037 (15.9%)
|
375 (16.1%)
|
0.863
|
|
|
Enterobacter spp.
|
237 (3.6%)
|
125 (5.4%)
|
<0.001
|
|
|
Other Enterobacteriaceae bacteria
|
495 (7.6%)
|
121 (5.2%)
|
<0.001
|
|
|
Non-fermenting bacteria
|
1 296 (19.9%)
|
647 (27.7%)
|
<0.001
|
|
|
Pseudomonas spp.
|
569 (8.7%)
|
236 (10.1%)
|
0.047
|
|
|
Acinetobacter spp.
|
487 (7.5%)
|
274 (11.7%)
|
<0.001
|
|
|
Burkholderia spp.
|
32 (0.5%)
|
17 (0.7%)
|
0.185
|
|
|
S. maltophilia
|
114 (1.7%)
|
61 (2.6%)
|
0.01
|
|
|
Other non-fermenting bacteria
|
94 (1.4%)
|
59 (2.5%)
|
<0.001
|
|
|
H. influenzae
|
150 (2.3%)
|
19 (0.8%)
|
<0.001
|
|
|
M. catarrhalis
|
45 (0.7%)
|
2 (0.1%)
|
<0.001
|
|
Other bacteria
|
|
215 (3.3%)
|
46 (2.0%)
|
0.001
|
Fungi
|
|
|
260 (4.0%)
|
196 (8.4%)
|
<0.001
|
|
Candida spp.
|
|
233 (3.6%)
|
185 (7.9%)
|
<0.001
|
|
Aspergillus spp.
|
|
20 (0.3%)
|
10 (0.4%)
|
0.386
|
|
Cryptococcus spp.
|
|
3 (0.0%)
|
0 (0.0%)
|
0.571*
|
|
Other fungi
|
|
4 (0.0%)
|
1 (0.0%)
|
0.854#
|
Abbreviations: SBA, specimen taken before antibiotic therapy; SAA, specimen taken after antibiotic therapy; S. aureus, Staphylococcus aureus; CNS, coagulase-negative Staphylococcus; E. coli, Escherichia coli; K. pneumoniae, Klebsiella pneumoniae; S. maltophilia, Stenotrophomonas maltophilia; H. influenzae, Haemophilus influenzae; M. catarrhalis, Moraxella catarrhalis.
*Fisher’s exact test
# Corrected chi-square test.
The proportion of bacteria in the SBA group was 96.0% (6 256 strains), higher than that of the SAA group (91.6%, 2 138 strains, P<0.001); while the proportion of fungi isolated from the SAA group was 8.4%, higher than that of the SBA group (4.0%, P<0.001). The ratio of gram-positive bacteria isolated from the SBA group was slightly more than that isolated from the SAA group (27.2% vs. 24.7%, P = 0.020), while separation rate of gram-negative bacteria was not statistically different between the two groups (65.5% vs. 64.9%, P = 0.607).
Gram-positive microorganisms
The percentage of Staphylococcus aureus (S. aureus) in the SAA group was higher than that in the SBA group (9.9% vs. 8.5% P = 0.041). In contrast, the isolation rates of coagulase-negative Staphylococcus (CNS)and Streptococcus spp. in the SBA group were higher than those in the SAA group (7.2% vs. 4.5% and 4.8% vs. 2.7% respectively, both P<0.001). No significant difference in Enterococcus spp. was observed between the two groups (P = 0.173).
Gram-negative microorganisms
The percentage of Enterobacteriaceae isolated from the SBA group was higher than that from the SAA group (42.6% vs. 36.3%, P<0.001). In contrast, the isolation rate of non-fermenting bacteria in the SBA group was lower than that in the SAA group with significant difference (19.9% vs. 27.7%, P<0.001). In the Enterobacteriaceae, the isolation rate of Escherichia coli (E. coli) in the SBA group was higher than that in the SAA group (15.5% vs. 9.7%, P<0.001), while the isolation rates of Enterobacter spp. in the SBA group was lower than those in the SAA group (3.6% vs. 5.4%, P<0.001). No significant difference in Klebsiella pneumoniae (K. pneumoniae) was observed between the two groups (P = 0.863).
As for non-fermenting bacteria, the isolation rates of Pseudomonas spp., Acinetobacter spp., and Stenotrophomonas maltophilia (S. maltophilia), were significantly lower in the SBA group than those in the SAA group (8.7% vs. 10.1%, 7.5% vs. 11.7%, and 1.7% vs. 2.6%, respectively, all P<0.05).
Although rarely isolated, the separation rates of Haemophilus influenzae (H. influenzae) and Moraxella catarrhalis (M. catarrhalis) between the two groups were significantly different (2.3% in the SBA group vs. 0.8% in the SAA group and 0.7% in the SBA group vs. 0.1% in the SAA group, respectively, both P<0.001).
Fungi
The isolation rate of Candida spp. in the SAA group was 7.9%, which was higher than that in the SBA group (3.6%, P<0.001). None of the other species had significant differences between the two groups.
Subgroup analysis
As a result of inconsistent sample composition between the two groups, which may lead to bias, we conducted subgroup analysis to compare the microorganism distribution according to the specimen types.
Respiratory secretions
Further analysis of respiratory secretions found that the microbial ratio was significantly different between the two groups. Fig 2 shows the descending order of the top 7 pathogens of the SBA group (dotted columns) corresponding to the proportion of these microorganisms in the SAA group (slanted lines columns). The ratios of Enterobacteriaceae (including K. pneumoniae, Serratia marcescens, Proteus mirabilis, E. coli, Enterobacter cloacae, etc.),, H. influenzae, M. catarrhalis isolated from the SBA group were significantly higher than those in the SAA group (all P<0.05). In contrast, the proportions of non-fermenting bacteria (including Acinetobacter baumannii, Pseudomonas aeruginosa, S. maltophilia, Burkholderia cepacia, etc.),, and Candida spp. isolated from the SBA group were significantly lower than those in the SAA group (all P<0.05). There were no statistical differences in the ratios of S. aureus and Streptococcus pneumoniae between the two groups.
Blood
Fig 3 shows the descending order of the top 7 pathogens of the SBA group (dotted columns) corresponding to the proportion of these microorganisms in the SAA group (slanted lines columns). There was a slight difference between the two groups. The ratios of Streptococcus spp. (including streptococcus viridans, Streptococcus angina, etc.) from the SBA group were significantly higher than those in the SAA group (P<0.05). The proportions of non-fermenting bacteria (including Acinetobacter baumannii, Pseudomonas aeruginosa, etc.) and Enterococcus spp. (including Enterococcus faecium, Enterococcus faecalis, etc)isolated from the SBA group were significantly lower than those in the SAA group (all P<0.05). But there was no statistically significant difference between the two groups in the isolation rates of CNS (including Staphylococcus epidermidis, Staphylococcus humanoidus, staphylococcus capitis, Staphylococcus haemolyticus, staphylococcus warneri, etc.),, Enterobacteriaceae (including K. pneumoniae, Serratia marcescens, Enterobacter cloacae, etc.), S. aureus and Candida spp..
Urine
Fig 4 shows the descending order of the top 7 pathogens of the SBA group (dotted columns) corresponding to the proportion of these microorganisms in the SAA group (slanted lines columns). The proportions of Enterobacteriaceae (including E. coli, K. pneumoniae, Proteus mirabilis, Enterobacter cloacae, etc.),, CNS (including Staphylococcus epidermidis, Staphylococcus haemolyticus, etc.) and Streptococcus spp. (including Streptococcus agalactiae, streptococcus viridans, etc.) isolated from the SBA group were significantly higher than those from the SAA group (all P<0.05). The proportions of non-fermenting bacteria (including Pseudomonas aeruginosa, Acinetobacter baumannii, etc.) and Candida spp. (including Candida albicans, Candida tropicalis, etc.)isolated from the SBA group were significantly lower than those of the SAA group (all P<0.05). There was no statistically significant difference found in the remaining microorganisms.
Body fluid specimens
There were no statistically significant differences in the isolation rates of top 7 major strains between the two groups, including Enterobacteriaceae (including E. coli, K. pneumoniae, Enterobacter cloacae, etc.),, Enterococcus spp., non-fermenting bacteria(including Pseudomonas aeruginosa, Acinetobacter baumannii, S. maltophilia, etc.),, CNS (including Staphylococcus epidermidis, staphylococcus sciuri, etc.),, Candida spp., S. aureus and Streptococcus spp. between the two groups.