Online Table I - Initial antibacterial therapy according to compliance with therapeutic recommendations and
phase of the study.
Retrospective
phase
N
Compliant with guidelines
Levofloxacin (~) monotherapy
Ceftriaxone or cefotaxime or cefepime + advanced macrolide
Amoxycillin/clavulanate (~) + advanced macrolide
Levofloxacin (~) + antipneumococcal beta-lactam (§)
Antianaerobe + levofloxacin (~) or amoxycillin/clavulanate (~)
Non-compliant with guidelines
Ceftriaxone or cefotaxime or cefepime monotherapy
Amoxycillin/clavulanate (~) monotherapy
Other monotherapies (†)
Antianaerobe monotherapy
Two-drug combinations with levofloxacin
Two-drug combinations with antipneumococcal beta-lactams (§)(†)
Other two-drug combinations (†)
Three-drug combinations (†)
Other combinations containing antianaerobes
(%)
Prospective
phase
N
(%)
476 (33.0)
616 (43.9)
150 (10.4)
164 (11.4)
78 (5.4)
80 (5.5)
4 (0.3)
214 (15.2)
167 (11.9)
152 (10.8)
76 (5.4)
7 (0.5)
967 (67.0)
788 (56.1)
254 (17.6)
209 (14.5)
245 (17.0)
2 (0.1)
52 (3.6)
83 (5.8)
96 (6.7)
14 (1.0)
12 (0.8)
198 (14.1)
169 (12.0)
184 (13.1)
0
55 (3.9)
54 (3.8)
105 (7.5)
6 (0.4)
17 (1.2)
~) or equivalent antibiotic of the same class.
§) ceftriaxone, cefotaxime, cefepime, amoxycillin/clavulanate or equivalent penicillin.
†) excluding antianaerobes or antianaerobe-containing combinations.
Online Table II -
Initial antibacterial therapy according to phase of the study: detail of therapies compliant
with therapeutic recommendations. Proportions < 1% are omitted.
Retrospective
phase
N
(%)
Prospective
phase
N
(%)
Levofloxacin (~) monotherapy
levofloxacin
moxifloxacin
150 (10.4)
150 (10.4)
0
214 (15.2)
213 (15.2)
1
Ceftriaxone or cefotaxime or cefepime + advanced macrolide
ceftriaxone + clarithromycin
ceftriaxone + azithromycin
cefotaxime + clarithromycin
cefotaxime + azithromycin
cefepime + clarithromycin
164 (11.4)
138 (9.6)
1
23 (1.6)
0
2
167 (11.9)
104 (7.4)
32 (2.3)
20 (1.4)
8
3
Amoxycillin/clavulanate (~) + advanced macrolide
amoxycillin/clavulanate + clarithromycin
amoxycillin/clavulanate + azithromycin
ampicillin/sulbactam + clarithromycin
ampicillin/sulbactam + azithromycin
ampicillin + clarithromycin
78
67
0
9
0
2
(5.4)
(4.6)
Levofloxacin (~) + antipneumococcal beta-lactam (§)
levofloxacin + amoxycillin/clavulanate
levofloxacin + ampicillin/sulbactam
levofloxacin + ceftriaxone
levofloxacin + cefotaxime
levofloxacin + cefepime
moxifloxacin + amoxycillin/clavulanate
80
40
4
19
17
0
0
(5.5)
(2.8)
Antianaerobe + levofloxacin or amoxycillin/clavulanate (~)
levofloxacin + metronidazole
levofloxacin + clindamycin
amoxycillin/clavulanate + metronidazole
ampicillin/sulbactam + clindamycin
(1.3)
(1.2)
4
1
0
3
0
~) or equivalent antibiotic of the same class.
§) ceftriaxone, cefotaxime, cefepime, amoxycillin/clavulanate or equivalent penicillin.
152 (10.8)
90 (6.4)
47 (3.3)
4
11
0
76
18
4
38
13
2
1
7
3
1
2
1
(5.4)
(1.3)
(2.7)
Online Table III -
Initial antibacterial therapy according to phase of the study: detail of monotherapies
non-compliant with therapeutic recommendations. Proportions < 1% are omitted.
Retrospective
phase
N
(%)
Prospective
phase
N
(%)
Ceftriaxone or cefotaxime or cefepime monotherapy
ceftriaxone
cefotaxime
cefepime
254 (17.6)
178 (12.3)
67 (4.6)
9
198 (14.1)
166 (11.8)
29 (2.1)
3
Amoxycillin/clavulanate (~) monotherapy
amoxycillin/clavulanate
ampicillin/sulbactam
amoxycillin
ampicillin
209 (14.5)
148 (10.3)
56 (3.9)
2
3
169 (12.0)
134 (9.5)
32 (2.3)
1
2
Other monotherapies (†)
ceftazidime
cefodizime
ceftizoxime
cephazolin
cefoxitin or cefonicid
cefixime
imipenem/cilastatin
piperacillin
piperacillin/tazobactam
ticarcillin/clavulanate
penicillin
ciprofloxacin
pefloxacin or lomefloxacin
clarithromycin
azithromycin
tobramycin
netilmicin
teicoplanin
trimethoprim/sulphamethoxazole
doxycycline
245 (17.0)
48 (3.3)
25 (1.7)
21 (1.5)
2
2
0
10
35 (2.4)
20 (1.4)
2
2
38 (2.6)
1
29 (2.0)
0
2
2
4
2
0
184 (13.1)
27 (1.9)
7
11
3
2
1
8
22 (1.6)
51 (3.6)
0
0
35 (2.5)
2
8
4
1
0
0
1
1
Antianaerobe monotherapy
clindamycin
metronidazole
~) or equivalent antibiotic of the same class.
†) excluding antianaerobes.
2
1
1
0
0
0
Online Table IVa -
Initial antibacterial therapy according to phase of the study: detail of combination
therapies non-compliant with therapeutic recommendations [1- continues]. Proportions < 1% are
omitted.
Retrospective
phase
Prospective
phase
N
(%)
N
(%)
Two-drug combinations with levofloxacin
levofloxacin + cefodizime
levofloxacin + ceftazidime
levofloxacin + ceftizoxime or ceftibuten or cefonicid
levofloxacin + piperacillin/tazobactam
levofloxacin + piperacillin
levofloxacin + imipenem/cilastatin or meropenem
levofloxacin + clarithromycin or azithromycin
levofloxacin + aminoglycoside
levofloxacin + teicoplanin
levofloxacin + other
52
14
8
4
10
2
3
8
3
0
0
(3.6)
(1.0)
55
15
8
2
8
4
2
10
0
3
3
(3.9)
(1.1)
Two-drug combinations with antipneumococcal beta-lactams (§)(†)
ceftriaxone + ciprofloxacin
ceftriaxone + amikacin
ceftriaxone + netilmicin
ceftriaxone + gentamicin
cefotaxime + ciprofloxacin
cefotaxime + aminoglycosides
amoxycillin/clavulanate + ciprofloxacin
amoxycillin/clavulanate + amikacin
amoxycillin/clavulanate + netilmicin
amoxycillin/clavulanate + gentamicin
ampicillin/sulbactam + ciprofloxacin
ceftriaxone or cefepime + teicoplanin
ampicillin/sulbactam + aminoglycosides
ceftriaxone + amoxycillin/clavulanate or ampicillin/sulbactam
miscellaneous
83
2
15
6
4
2
5
14
4
6
2
3
3
6
3
8
(5.8)
54
10
7
0
0
3
4
11
4
1
2
1
0
3
3
5
(3.8)
(1.0)
(1.0)
§) ceftriaxone, cefotaxime, cefepime, amoxycillin/clavulanate or equivalent penicillin.
†) excluding antianaerobe-containing combinations.
Online Table IVb -
Initial antibacterial therapy according to phase of the study: detail of combination
therapies non-compliant with therapeutic recommendations [2- continuation]. Proportions < 1% are
omitted.
Retrospective
phase
Prospective
phase
N
(%)
N
(%)
Other two-drug combinations (†)
ceftazidime + clarithromycin or azithromycin
ceftizoxime or cefodizime + clarithromycin or azithromycin or roxithromycin
cephazolin + clarithromycin or azithromycin
cefoxitin + clarithromycin or azithromycin
imipenem/cilastatin or meropenem + clarithromycin or azithromycin
piperacillin/tazobactam + clarithromycin or azithromycin
piperacillin + clarithromycin
ticarcillin/clavulanate + clarithromycin
ceftazidime + ciprofloxacin
ceftizoxime or cefodizime or cefonicid + ciprofloxacin
imipenem/cilastatin + ciprofloxacin
piperacillin/tazobactam or ticarcillin/clavulanate + ciprofloxacin
piperacillin + ciprofloxacin
ceftazidime + aminoglycosides
ceftizoxime or cefodizime or cefoxitin + aminoglycosides
imipenem/cilastatin or meropenem + aminoglycosides
piperacillin/tazobactam + aminoglycosides
piperacillin + aminoglycosides
ciprofloxacin + clarithromycin
clarithromycin + aminoglycosides
ceftazidime + teicoplanin or vancomycin
imipenem/cilastatin + teicoplanin
piperacillin/tazobactam + teicoplanin
amikacin + teicoplanin or vancomycin
clarithromycin or azithromycin + teicoplanin or vancomycin
miscellaneous
96
13
3
4
1
6
11
3
3
2
3
2
4
2
7
2
4
5
4
3
3
4
2
0
0
1
4
(6.7)
105
19
4
2
2
1
20
1
0
4
2
1
3
1
6
5
1
6
1
4
5
2
1
1
7
2
4
(7.5)
(1.4)
Three-drug combinations (†)
ceftriaxone or cefotaxime + clarithromycin + aminoglycoside
miscellaneous
14
4
10
(1.0)
6
0
6
(0.4)
Other combinations containing antianaerobes
aztreonam + clindamycin
antipneumococcal beta-lactam + clindamycin
antipneumococcal beta-lactam + metronidazole
other + clindamycin (two-drug combinations)
other + metronidazole (two-drug combinations)
other + aztreonam + clindamycin (three-drug combinations)
others + metronidazole (three-drug combinations)
12
4
1
2
1
1
2
1
17
6
3
2
2
1
0
3
(1.2)
(1.4)
†) excluding antianaerobe-containing combinations.
Online Table V -
Outcome of first therapy cycle according to study phase, Fine score, and antibacterial treatment in the previous 2 weeks.
Factor
Level
Success rate
N (%)
Study phase
Retrospective
Prospective
Fine score (°)
90-100 to >200
Previous antibacterial
treatment
No
Yes
1031 /1441 (71.5)
1034 /1400 (73.9)
1714 /2307 (74.3)
345 / 526 (65.6)
Unadjusted
RR (*)
OR (*)
0.92
1.34
Adjusted (a)
OR (*) (95%CI)
P (^)
0.89
0.83 (0.69 - 1.00)
0.049
1.30
1.30 (1.25 - 1.34) <0.0001
1.52
1.46 (1.16 - 1.84)
0.002
a) for all other factors in this table (fixed effects) and Center (random effect).
*) risk ratio (RR) and odds ratio (OR) for failure versus first level.
^) Wald chi-square test (multiple logistic regression).
°) as numerical variable on a 10-unit scale; OR is estimated for each 10-unit increase over the whole range of values.
Online Table VI -
Outcome of first therapy cycle according to study phase, Fine score, and antibacterial treatment in the previous 2 weeks. Sensitivity analysis
excluding patients from nursing residence.
Factor
Level
Success rate
N (%)
Study phase
Fine score (°)
Previous antibacterial
treatment
Retrospective
Prospective
912 /1245 (73.3)
913 /1215 (75.1)
Unadjusted
RR (*)
OR (*)
0.93
0.91
0.86 (0.70 - 1.05)
1.31
1.30 (1.25 - 1.36) <0.0001
1.50
1.47 (1.15 - 1.90)
91-100 (class IV)
No
Yes
1519 /2008 (75.6)
301 / 446 (67.5)
Adjusted (a)
1.34
OR (*) (95%CI)
P (^)
0.14
0.004
a) for all other factors in this table (fixed effects) and Center (random effect).
*) risk ratio (RR) and odds ratio (OR) for failure versus first level.
^) Wald chi-square test (multiple logistic regression).
°) as numerical variable on a 10-unit scale; OR is estimated for each 10-unit increase over the whole range of values.
Online Table VII -
Success rates at the end of first therapy cycle by study phase and compliance with therapeutic recommendations.
Non-compliant
Compliant
N (%)
N (%)
Retrospective phase
677 / 966 (70.1)
354 / 475 (74.5)
Prospective phase
554 / 786 (70.5)
480 / 614 (78.2)
P-value for interaction
(logistic regression)
0.31 (unadjusted)
0.33 (adjusted) (*)
*) for Fine score (as numerical variable on a 10-unit scale) and previous antibacterial treatment (yes/no).
Online Table VIII -
Outcome of first therapy cycle according to study phase, Fine score, antibacterial treatment in the previous 2 weeks, and compliance with
therapeutic recommendations.
Factor
Level
Success rate
N (%)
Unadjusted
RR (*)
OR (*)
Adjusted (a)
OR (*) (95%CI)
P (^)
Compliance with
therapeutic guidelines
No
Yes
1231 /1752 (70.3)
834 /1089 (76.6)
0.79
0.72
0.74 (0.60 - 0.90)
0.004
Study phase
Retrospective
Prospective
1031 /1441 (71.5)
1034 /1400 (73.9)
0.92
0.89
0.86 (0.71 - 1.03)
0.10
1.30
1.29 (1.25 - 1.34) <0.0001
1.52
1.47 (1.16 - 1.85)
Fine score (°)
90-100 to >200
Previous antibacterial
treatment
No
1714 /2307 (74.3)
Yes
345 / 526 (65.6)
1.34
0.002
a) for all other factors in this table (fixed effects) and Center (random effect).
*) risk ratio (RR) and odds ratio (OR) for failure versus first level.
^) Wald chi-square test (multiple logistic regression).
°) as numerical variable on a 10-unit scale; OR is estimated for each 10-unit increase over the whole range of values.
Online Table IX -
Outcome of first therapy cycle according to study phase, Fine score, antibacterial treatment in the previous 2 weeks, and compliance with
therapeutic recommendations. Sensitivity analysis excluding patients from nursing residence.
Factor
Level
Success rate
N (%)
Compliance with
therapeutic guidelines
No
Yes
Study phase
Retrospective
Prospective
Fine score (°)
91-100 to >200
Previous antibacterial
treatment
No
Yes
Unadjusted
RR (*)
OR (*)
1073 /1497 (71.7)
752 / 963 (78.1)
0.77
912 /1245 (73.3)
913 /1215 (75.1)
0.93
1519 /2008 (75.6)
301 / 446 (67.5)
1.34
Adjusted (a)
OR (*) (95%CI)
P (^)
0.71
0.72 (0.58 - 0.89)
0.004
0.91
0.89 (0.72 - 1.09)
0.24
1.31
1.30 (1.25 - 1.36) <0.0001
1.50
1.48 (1.15 - 1.90)
0.004
a) for all other factors in this table (fixed effects) and Center (random effect).
*) risk ratio (RR) and odds ratio (OR) for failure versus first level.
^) Wald chi-square test (multiple logistic regression).
°) as numerical variable on a 10-unit scale; OR is estimated for each 10-unit increase over the whole range of values.
Online Table X -
Mortality during first therapy cycle according to study phase, Fine score, and antibacterial treatment in the previous 2 weeks.
Factor
Level
Death rate
N (%)
Study phase
Retrospective
Prospective
Fine score (°)
91-100 to >200
Previous antibacterial
treatment
No
Yes
179 /1443 (12.4)
162 /1404 (11.5)
268 /2312 (11.6)
72 / 527 (13.7)
Unadjusted
Adjusted (a)
RR (*)
OR (*)
0.93
0.92
0.81 (0.63 - 1.06)
1.37
1.43 (1.36 - 1.50) <0.0001
1.21
1.26 (0.91 - 1.75)
1.18
OR (*) (95%CI)
P (^)
0.12
0.15
a) for all other factors in this table (fixed effects) and Center (random effect).
*) risk ratio (RR) and odds ratio (OR) for death versus first level.
^) Wald chi-square test (multiple logistic regression).
°) as numerical variable on a 10-unit scale; OR is estimated for each 10-unit increase over the whole range of values.
Online Table XI -
Mortality during first therapy cycle according to study phase, Fine score, and antibacterial treatment in the previous 2 weeks. Sensitivity
analysis excluding patients from nursing residence.
Factor
Level
Death rate
N (%)
Study phase
Retrospective
Prospective
Fine score (°)
91-100 to >200
Previous antibacterial
treatment
No
Yes
132 /1247 (10.6)
119 /1219 (9.8)
197 /2013 (9.8)
54 / 447 (12.1)
Unadjusted
Adjusted (a)
RR (*)
OR (*)
0.92
0.91
0.80 (0.59 - 1.09)
1.37
1.44 (1.36 - 1.53) <0.0001
1.27
1.42 (0.98 - 2.07)
1.23
OR (*) (95%CI)
P (^)
0.15
0.065
a) for all other factors in this table (fixed effects) and Center (random effect).
*) risk ratio (RR) and odds ratio (OR) for death versus first level.
^) Wald chi-square test (multiple logistic regression).
°) as numerical variable on a 10-unit scale; OR is estimated for each 10-unit increase over the whole range of values.
Online Table XII -
Mortality during first therapy cycle by study phase and compliance with therapeutic recommendations.
Non-compliant
Compliant
N (%)
N (%)
Retrospective phase
126 / 967 (13.0)
53 / 476 (11.1)
Prospective phase
108 / 788 (13.7)
54 / 616
P-value for interaction
(logistic regression)
(8.8)
0.19 (unadjusted)
0.22 (adjusted) (*)
*) for Fine score (as numerical variable on a 10-unit scale) and previous antibacterial treatment (yes/no).
Online Table XIII -
Mortality during first therapy cycle according to study phase, Fine score, antibacterial treatment in the previous 2 weeks, and compliance
with therapeutic recommendations.
Factor
Level
Death rate
N (%)
Unadjusted
RR (*)
OR (*)
Adjusted (a)
OR (*) (95%CI)
P (^)
Compliance with
therapeutic guidelines
No
Yes
234 /1755 (13.3)
107 /1092 (9.8)
0.73
0.71
0.77 (0.58 - 1.04)
0.082
Study phase
Retrospective
Prospective
179 /1443 (12.4)
162 /1404 (11.5)
0.93
0.92
0.84 (0.64 - 1.10)
0.19
1.37
1.43 (1.35 - 1.50) <0.0001
1.21
1.27 (0.91 - 1.76)
Fine score (°)
90-100 to >200
Previous antibacterial
treatment
No
268 /2312 (11.6)
Yes
72 / 527 (13.7)
1.18
0.15
a) for all other factors in this table (fixed effects) and Center (random effect).
*) risk ratio (RR) and odds ratio (OR) for death versus first level.
^) Wald chi-square test (multiple logistic regression).
°) as numerical variable on a 10-unit scale; OR is estimated for each 10-unit increase over the whole range of values.
Online Table XIV -
Mortality during first therapy cycle according to study phase, Fine score, antibacterial treatment in the previous 2 weeks, and compliance
with therapeutic recommendations. Sensitivity analysis excluding patients from nursing residence.
Factor
Level
Death rate
N (%)
Unadjusted
RR (*)
OR (*)
Adjusted (a)
OR (*) (95%CI)
P (^)
Compliance with
therapeutic guidelines
No
Yes
172 /1500 (11.5)
79 / 966 (8.2)
0.71
0.69
0.74 (0.53 - 1.03)
0.076
Study phase
Retrospective
Prospective
132 /1247 (10.6)
119 /1219 (9.8)
0.92
0.91
0.83 (0.61 - 1.13)
0.23
1.37
1.44 (1.35 - 1.52) <0.0001
1.27
1.43 (0.98 - 2.07)
Fine score (°)
91-100 to >200
Previous antibacterial
treatment
No
Yes
197 /2013
(9.8)
54 / 447 (12.1)
1.23
0.063
a) for all other factors in this table (fixed effects) and Center (random effect).
*) risk ratio (RR) and odds ratio (OR) for death versus first level.
^) Wald chi-square test (multiple logistic regression).
°) as numerical variable on a 10-unit scale; OR is estimated for each 10-unit increase over the whole range of values.