TABLE 1

Characteristics and primary outcomes of the studies included in the meta-analysisa

First author, yr (reference)Study design, countryNo. of CE pts, patient setting, severity of pneumoniaCausative pathogen (no. of pts)RegimenTime of clinical evaluationNo. of patients assessed/no. with clinical cure (%)Time of mortality assessmentNo. of patients assessed/no. who died (%)
Short courseLong courseShort courseLong courseShort courseLong course
Masiá, 2017 (28)Nonrandomized double-blind clinical trial with historical control, Spain253, outpatients, Fine I/IIbStreptococcus pneumoniae (47), Mycoplasma pneumoniae (33), Haemophilus influenzae (6), Legionella pneumophila (5), Chlamydophila pneumoniae (4), Klebsiella pneumoniae (1)Azithromycin, 500 mg/day p.o. for 5 daysLevofloxacin, 500 mg/day p.o. for 7 daysEOT207/216 (95.8)35/37 (94.6)30-day0/216 (0)0/37 (0)
Zhao, 2016 (27)MC open-label RCT, China427, inpatients/outpatients, mild to moderate with CURB65c score of 0–2, 87% of which had a CURB65 score of 0S. pneumoniaeLevofloxacin, 750 mg/day i.v. for 5 daysLevofloxacin, 500 mg/day i.v./p.o. for at least 7 days (range, 7–14 days)EOT195/208 (93.8)210/219 (95.9)NANRNR
Paris, 2008 (20)MC open-label RCT, Italy267, outpatients, mild to moderate with Fine I/IIM. pneumoniae (47), C. pneumoniae (23), H aemophilus parainfluenzae (17), H. influenzae (16), Staphylococcus aureus (15), S. pneumoniae (4), Moraxella catarrhalis (3), Acinetobacter spp. (6)Azithromycin, 1 g/day p.o. for 3 daysAmoxicillin-clavulanic acid, 875/125 mg b.i.d. p.o. for 7 daysEOT (days 8–12)126/136 (92.6)122/131 (93.1)NANRNR
File, 2007 (15)MCd double-blind RCT483, outpatients, mild to moderate with Fine ≤IIIS. pneumoniae (66), C. pneumoniae (49), M. pneumoniae (45), H. influenzae (40), S. aureus (38)Gemifloxacin, 320 mg/day p.o. for 5 daysGemifloxacin, 320 mg/day p.o. for 7 daysEOT (days 7–9)236/247 (95.5)226/236 (95.8)NANRNR
el Moussaoui, 2006 (14)MC double-blind RCT, Netherlands114, inpatients, mild to moderate-severeS. pneumoniae (37), H. influenzae (10), M. catarrhalis (4), influenza A or B virus (4), C. pneumoniae (2), H. parainfluenzae (1), other (4)Amoxicillin, i.v. for 3 daysAmoxicillin i.v. for 3 days followed by amoxicillin p.o. for 5 daysDay 1050/54 (92.6)56/60 (93.3)NANRNR
D'Ignazio, 2005 (11)MCe double-blind RCT363, outpatients, mild to moderate with Fine I–IIIS. aureus (43), H. parainfluenzae (35), S. pneumoniae (28), H. influenzae (26), M. catarrhalis (10)Azithromycin, single 2.0-g dose of microspheres p.o.Levofloxacin, 500 mg/day p.o. for 7 daysDays 14–21156/174 (89.7)177/189 (93.7)All cause1/174 (0.6)2/189 (1.1)
Drehobl, 2005 (12)MCf double-blind RCT411, outpatients, mild to moderate with Fine I/IIC. pneumoniae (52), M. pneumoniae (47), S. pneumoniae (46), H. influenzae (41), M. catarrhalis (13)Azithromycin, single 2.0-g dose of microspheres p.o.Clarithromycin, 500 mg extended-release formulation b.i.d. p.o. for 7 daysDays 14–21187/202 (92.6)198/209 (94.7)NANRNR
Rahav, 2004 (21)MC open-label RCT, Israel108, outpatientsNRAzithromycin, 500 mg/day p.o. for 3 daysErythromycin, amoxicillin-clavulanic acid, roxithromycin, cefuroxime, amoxicillin, doxycycline, or cefaclor, p.o. for 10 daysDays 10–1461/62 (98.4)40/46 (87)NANRNR
Sopena, 2004 (25)MC open-label RCT, Spain63, inpatients/outpatients, mild to moderateM. pneumoniae (6), S. pneumoniae (4), L. pneumophila (4), H. influenzae (2), Coxiella burnetii (2), C. pneumoniae (1)Azithromycin, 500 mg/day p.o. for 3 daysClarithromycin, 250 mg b.i.d. p.o. for at least 10 days (range, 10–14 days)Days 10–1318/31 (58.1)22/32 (68.8)NANRNR
Tellier, 2004 (26)MCg double-blind RCT466, inpatients/outpatients, Fine I–VS. pneumoniae (80), H. influenzae (67), M. catarrhalis (10)Telithromycin, 800 mg/day p.o. for 5 daysClarithromycin, 500 mg b.i.d. p.o. for 10 daysDays 17–21142/159 (89.3)134/146 (91.8)All cause1/159 (0.6)2/146 (1.4)
Dunbar, 2003 (13)MC double-blind RCT, United States390, inpatients/outpatients, Fine I–VM. pneumoniae (79), S. pneumoniae (42), C. pneumoniae (38), H. influenzae (27), H. parainfluenzae (22), L. pneumophila (14)Levofloxacin, 750 mg/day i.v./p.o. for 5 daysLevofloxacin, 500 mg/day i.v./p.o. for 10 daysDays 7–14183/198 (92.4)175/192 (91.1)All cause (between days 31 and 38)5/256 (2)9/265 (3.4)
Sánchez, 2003 (29)Open-label nonrandomized clinical trial, Spain603, inpatients, Fine III–VC. pneumoniae (68), S. pneumoniae (62), viruses (37), L. pneumophila (31), C. burnetii (19), M. pneumoniae (16), Enterobacteriaceae (6), H. influenzae (3), S. aureus (1), S treptococcus pyogenes (1)Ceftriaxone, 1 g for 3 days, followed by oral amoxicillin-clavulanic acid, 875/125 mg p.o. t.i.d.), + azithromycin, 500 mg/day p.o. for 3 daysCeftriaxone, 1 g for 3 days, followed by oral amoxicillin-clavulanic acid, 875/125 mg p.o. t.i.d.), + clarithromycin, 500 mg b.i.d. i.v./p.o. for at least 10 daysNANRNRIn hospital14/383 (3.7)16/220 (7.3)
Léophonte, 2002 (18)MC double-blind RCT, France186, inpatientsFrom bronchial secretions, S. pneumoniae (18), H. influenzae (13), M. catarrhalis (4), K. pneumoniae (2), Pseudomonas aeruginosa (1)Ceftriaxone, 1 g/day i.v. for 5 daysCeftriaxone, 1 g/day i.v. for 5 days, followed by ceftriaxone, 1 g/day i.m. for 5 daysDay 1077/94 (81.9)76/92 (82.6)All cause4/94 (4.3)7/92 (7.6)
O'Doherty, 1998 (19)MCh open-label RCT196, outpatients, mild to moderateH. influenzae (34), S. pneumoniae (22), M. catarrhalis (9), S. aureus (2)Azithromycin, 500 mg/day p.o. for 3 daysClarithromycin, 250 mg b.i.d. p.o. for 10 daysEOT (12–16 days)57/88 (64.8)61/88 (69.3)NANRNR
Gris, 1996 (16)MC double-blind RCT, Belgium6, outpatientsNR separately for pneumoniaAzithromycin, 500 mg/day p.o. for 3 daysAmoxicillin-clavulanic acid, 500 mg/125 mg t.i.d. p.o. for 10 daysEOT (12–16 days)2/2 (100)1/4 (25)NANRNR
Schönwald, 1994 (23)MC open-label RCT, Croatia150, inpatients with atypical pneumoniaM. pneumoniae (104), Chlamydia psittaci (18), C. burnetii (4), unknown (16)Azithromycin, 500 mg/day p.o. for 3 daysRoxithromycin, 150 mg b.i.d. p.o. for 10 daysDays 13–1588/89 (98.9)50/53 (94.3)NANRNR
Bohte, 1995 (9)MC open-label RCT, Netherlands104, inpatientsS. pneumoniae (26), viruses (9), M. pneumoniae (8), L. pneumophila (4), H. influenzae (3), Streptococcus spp. (3), Chlamydia spp. (2), M. catarrhalis (1)Azithromycin, 500 mg b.i.d. on day 1, followed by 500 mg q.d. on days 2–5, or benzylpenicillin, i.v. 1 × 106 IU q.d. for 5 daysErythromycin, 500 mg q.d. p.o. for 10 daysDays 12–1552/83 (62.7)14/21 (66.7)NANRNR
Rizzato, 1995 (22)Open-label RCT, Italy40, inpatients, low to moderately severeM. pneumoniae (9), L. pneumophila (5), C. pneumoniae (3), C. pneumoniae/K. pneumoniae (1), H. parainfluenzae (2), H. influenzae (1), S. pneumoniae (1), unknown (18)Azithromycin, 500 mg/day p.o. for 3 daysClarithromycin, 250 mg b.i.d. p.o. for at least 8 days (10 ± 2)NR20/20 (100)17/20 (85)NANRNR
Kinasewitz, 1991 (17)MC double-blind RCT, United States71, NRS. pneumoniae (30), H. influenzae (25), H. parainfluenzae (10), S. aureus (10), K. pneumoniae (5), M. catarrhalis (4), other Enterobacteriaceae (9), other (7)Azithromycin, 500 mg p.o. on day 1 followed by 250 mg/day p.o. on days 2–5Cefaclor, 500 mg t.i.d. p.o. for 10 daysDays 10–1315/32 (46.9)16/39 (41)All cause1/32 (3.1)2/39 (5.1)
Brion, 1990 (10)MC open-label RCT, France89, outpatientsS. pneumoniae (15), M. pneumoniae (4), H. influenzae (3), C. psittaci (2), L. pneumophila (2), S. aureus (1), other (4)Azithromycin, 500 mg p.o. on day 1 followed by 250 mg/day p.o. on days 2–5Josamycin, 1 g b.i.d. p.o. for 10 daysDay 3037/46 (80.4)38/43 (88.4)All cause3/46 (6.5)3/43 (7)
Schönwald, 1990 (24)MCi open-label RCT71, inpatients/outpatients with atypical pneumoniaM. pneumoniae (55), C. psittaci (16)Azithromycin, 250 mg b.i.d. on day 1 followed by 250 mg/day on days 2–5Erythromycin, 500 mg q.d. for 10 daysNR39/39 (100)32/32 (100)NANRNR
  • a Abbreviations: CE, clinically evaluable; MC, multicenter; RCT, randomized controlled trial; pts, patients; EOT, end of treatment; NR, not reported; NA, not applicable; i.v., intravenously; p.o., per os; i.m., intramuscularly; q.d., once a day; b.i.d., twice a day; t.i.d., three times a day; IU, international units.

  • b According to the pneumonia severity index (PSI)/PORT scoring system.

  • c The scoring system for assessing the risk for mortality in pneumonia.

  • d Sixty-eight centers in 9 countries: Bulgaria, Croatia, Czech Republic, Lithuania, Poland, Romania, Russia, Ukraine, and the United States.

  • e Fifty-six centers in 8 countries: Canada, Chile, India, Lithuania, Mexico, Peru, Russia, and the United States.

  • f Fifty-eight centers in 7 countries: the United States, Canada, Argentina, Russia, India, Estonia, and Lithuania.

  • g Seventy-seven centers in 9 countries: Argentina, Brazil, Canada, Chile, Germany, Republic of South Africa, Spain, the United Kingdom, and the United States.

  • h Twenty-eight centers in 4 countries.

  • i The centers which participated in this study are not reported.