Comparison 1. Atypical versus non‐aytpical.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality per antibiotic (ABX) treatment	25	5444	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.84, 1.55]
1.1 Quinolone (atypical arm)	19	3698	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.69, 1.39]
1.2 Macrolide (atypical arm)	4	540	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.52, 3.01]
1.3 Combined quinolone and macrolide (atypical arm)	1	808	Risk Ratio (M‐H, Fixed, 95% CI)	2.29 [0.81, 6.44]
1.4 Pristinamycine (atypical arm)	1	398	Risk Ratio (M‐H, Fixed, 95% CI)	1.98 [0.37, 10.69]
2 Mortality per age	25	5444	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.84, 1.55]
2.1 Mean age under 65 years old	15	3820	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [0.75, 1.94]
2.2 Mean age over 65 years old	8	1439	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.72, 1.69]
2.3 Data unavailable	2	185	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.34, 2.93]
3 Mortality ‐ per geographical area	25	5444	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.84, 1.55]
3.1 Europe	14	3209	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.79, 1.89]
3.2 North America	3	232	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [0.52, 3.86]
3.3 Other	8	2003	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.62, 1.60]
4 Mortality per allocation generation	25	5444	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.84, 1.55]
4.1 A	10	1953	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.68, 1.68]
4.2 B	15	3491	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.79, 1.81]
4.3 C	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Mortality per allocation concealment	25	5444	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.84, 1.55]
5.1 A	7	1590	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.66, 1.65]
5.2 B	18	3854	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.81, 1.83]
5.3 C	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Mortality per blinding	25	5444	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.84, 1.55]
6.1 Non‐blinded	16	2290	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.72, 1.50]
6.2 Single‐blind	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.3 Double or triple‐blind	9	3154	Risk Ratio (M‐H, Fixed, 95% CI)	1.37 [0.79, 2.38]
7 Mortality ‐ ITT analysis	12	2143	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.70, 2.15]
7.1 ITT (type 1)	12	2143	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.70, 2.15]
8 Clinical failure per antibiotic (ABx) treatment	28	5419	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.84, 1.04]
8.1 Quinolone (atypical arm)	21	3704	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.79, 1.02]
8.2 Macrolide (atypical arm)	5	536	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.76, 1.62]
8.3 Combined quinolone and macrolide (atypical arm)	1	808	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.75, 1.17]
8.4 Pristinamycine (atypical arm)	1	371	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.77, 1.81]
9 Clinical failure per age	28	5419	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.84, 1.04]
9.1 Mean age under 65 years old	15	3554	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.81, 1.06]
9.2 Mean age over 65 years old	8	1439	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.75, 1.10]
9.3 Data unavailable	5	426	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.77, 1.50]
10 Clinical failure per geographical area	28	5419	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.84, 1.04]
10.1 Europe	15	3084	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.74, 0.98]
10.2 North America	3	232	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.59, 1.45]
10.3 Other	10	2103	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.90, 1.24]
11 Clinical failure per allocation generation	28	5419	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.84, 1.04]
11.1 A	10	1878	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.82, 1.19]
11.2 B	17	3467	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.79, 1.02]
11.3 C	1	74	Risk Ratio (M‐H, Fixed, 95% CI)	7.29 [0.41, 130.64]
12 Clinical failure per allocation concealment	28	5419	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.84, 1.04]
12.1 A	7	1583	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.82, 1.19]
12.2 B	20	3762	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.80, 1.02]
12.3 C	1	74	Risk Ratio (M‐H, Fixed, 95% CI)	7.29 [0.41, 130.64]
13 Clinical failure per blinding	28	5419	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.84, 1.04]
13.1 Non‐blinded	18	2415	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.77, 1.05]
13.2 Single‐blind	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
13.3 Double or triple‐blind	10	3004	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.84, 1.11]
14 Clinical failure ‐ ITT analysis	28	5682	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.85, 1.02]
14.1 ITT studies (type 1)	7	1232	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.76, 1.12]
14.2 Dropouts assumed as failure (type 2)	15	3849	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.84, 1.05]
14.3 Non‐ITT, dropouts cannot be calculated (type 3)	6	601	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.63, 1.15]
15 Clinical failure ‐ pneumococcal pneumonia	18	1021	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.88, 1.70]
16 Clinical failure ‐ atypical pathogens	4	158	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.24, 1.10]
17 Clinical failure ‐ Legionella pneumophilae	5	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.05, 0.63]
18 Clinical failure per sponsorship	28	5419	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.84, 1.04]
18.1 Sponsored trials	21	4540	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.86, 1.08]
18.2 Non‐sponsored trials	3	288	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.64, 1.62]
18.3 Unclear sponsorship	4	591	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.49, 0.93]
19 Bacteriological failure	21	2310	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.65, 0.98]
19.1 Overall	21	2310	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.65, 0.98]
20 Bacteriological failure per allocation generation	21	2310	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.65, 0.98]
20.1 A	8	708	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.61, 1.32]
20.2 B	13	1602	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.59, 0.96]
21 Adverse events ‐ total	24	4918	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.93, 1.13]
22 Adverse events ‐ gastrointestinal events	16	4129	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.53, 0.92]
23 Adverse events ‐ requiring discontinuation of treatment	12	3806	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.72, 1.41]