Table 1.
Main Characteristics of the Studies Included in the Analysis
| Number of Patients With Legionellosis | Agent(s) Used (n) With Dosage and Duration | Mean Age, years | Proportion of Men, % | Underlying Disease, n (%) | Fine Score ≥4, n (%) | Treatment in ICU, n (%) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study | Study Design | Place of Study | Setting | Q | M | Q | M | Q | M | Q | M | Q | M | Q | M | Q | M | Risk-of-Bias Score |
| Dournon 1990 [27] | Retrospective observational study | France | Multicenter | 7 | 20 | PEF, 0.8 g/day | ERY, 0.8 g/day | NR | 49.8 | NR | 70 | NR | NR | NR | NR | NR | NR | 22 |
| Lode 1995 [28] | Randomized controlled trial | France, Germany, Italy, UK, Belgium, Greece, Israel, Netherlands, and Spain | Multicenter | 1 | 7 | SPX, 400 mg loading followed by 200 mg every morning; range, 1–16 days | ERY, 1000 mg b.i.d; range, 1–16 days | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | 25 |
| Gacouin 2002 [29] | Retrospective observational study | France | Single-center, ICU | 3 | 2 | OFX, 0.4 g/day | ERY, 3–4 g/day | NR | NR | NR | NR | NR | NR | NR | NR | 3 (100) | 2 (100) | 20 |
| Sokol 2002 [30] | Randomized controlled trial | USA | Multicenter | 7 | 7 | TVA, 200 mg q.d. for 7 days | CLR, 500 mg 2 tablets q.d for 7 days | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | 25 |
| Fogarty 2004 [31] | Randomized controlled trial | USA | Multicenter | 5 | 11 | LVX, 500 mg iv every 24 hours for 7–14 days | ERY, 500–1000 mg q6h iv + ceftriaxone 1–2 g iv or im q24h and then switched to CLR 500 mg po b.i.d. + amoxiclav 875 mg po b.i.d. for 7–14 days | NR | NR | NR | NR | NR | NR | NR | NR | 5 (100) | 11 (100) | 24 |
| Blázquez Garrido 2005 [18] | Prospective observational study | Spain | Single-center | 143 | 65 | LVX, mean total dosage 4.5 g | AZM (35), mean total dosage 4.5 g; CLR (30), mean total dosage 4.5 g | NR | NR | NR | NR | NR | NR | 29 (20.3) | 11 (16.9) | NR | NR | 21 |
| Querol- Ribelles 2005 [32] | Prospective observational study | Spain | Single-center | 8 | 3 | LVX, 500 mg o.d (except first 24 hours—2 doses given) | Ceftrioxone 2 g iv q24h + CLR 500 mg q12h iv or orally | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | 22 |
| Mykietiuk 2005 [33] | Prospective observational study | Spain | Single-center | 40 | 80 | LVX, 500 mg iv q.d. for 11.1 ± 6.39 days | ERY, 1000 mg iv q.i.d.; CLR, 500 mg iv b.i.d for 15.44 ± 7.83 days | 57.5 | 56 | 90 | 86.2 | NR | NR | 17 (42.5) | 38 (47.5) | 5 (12.5) | 2 (2.5) | 23 |
| Sabrià 2005 [34] | Prospective observational study | Spain and Andorra | Multicenter | 54 | 76 | LVX (50), 500 mg q12h till apyrexia; thereafter, 400 mg; 500 mg q.d., OFX, (4) 400 mg q12h for >14 days | ERY, 500 to 1000 mg q6h; CLR, 500 mg q12h for >14 days | 57.4 | 60 | 66.6 | 81.5 | 37 (68.5) | 59 (77.6) | NR | NR | 6 (11.1) | 9 (11.8) | 21 |
| Falcó 2006 [35] | Prospective observational study | Spain | Single-center | 18 | 95 | LVX for 10–14 days | CLR (52) for 14–21 days, AZM (43) for 5–10 days | 57.8 | 60.05 | 72.2 | 71.57 | NR | NR | 6 (37.5) | 37 (38.94) | 4 (22.2) | 12 (12.63) | 22 |
| Haranaga 2007 [36] | Retros pective observational study | Japan | Multicenter | 9 | 18 | CIP, 7 patients 300 mg b.i.d., 2 patients with renal failure, 300 mg q.d., 1 patient severe 600 mg b.i.d. for 15.3 days | ERY, 500 mg q6h/ q8h for 21.4 days | 69.7 | 62.8 | 67 | 78 | 8 (88.9) | 12 (66.7) | 6 (66.7) | 9 (50.0) | NR | NR | 21 |
| Nakamura 2009 [37] | Retros pective observational study | Japan | Multicenter | 12 | 4 | CIP (10), PAZ (2) | NR | NR | NR | NR | NR | NR | NR | 5 (41.7) | 2 (50.0) | NR | NR | 17 |
| Griffin 2010 [38] | Retros pective observational study | 14 countries (patients identified from CAPO international database) | Multicenter | 17 | 23 | LVX | AZM (13), CLR (10) | NR | NR | 81.3 | 73.9 | NR | NR | 7 (41.2) | 14 (60.9) | 3 (18.8) | 5 (21.7) | 21 |
| Viasus 2013 [39] | Prospective observational study | Spain | Multicenter | 111 | 74 | LVX 500 mg iv/day for 14 days (IQR, 21–28) | ERY (48) 500 mg iv/ day, CLR (24) 500 mg q.d, AZM (1), RXM (1) for 25 days (IQR, 21–28) | NR | NR | NR | NR | NR | NR | NR | NR | 38 (17.8) | 19 | |
| Rello 2013 [40] | Prospective observational study | Spain | Multicenter, ICU | 4 | 4 | LVX | CLR | NR | NR | NR | NR | NR | NR | NR | NR | 4 (100) | 4 (100) | 19 |
| Nagel 2014 [17] | Retrospective observational study | USA | Single-center | 21 | 20 | NR | AZM | 50.67 | 52.65 | 66.7 | 50 | NR | NR | NR | NR | 10 (47.6) | 5 (25) | 22 |
| Gershengorn 2015 [6] | Retrospective observational study | USA | Multicenter | 908 | 1073 | LVX (337), high dose 750 mg; others (571) standard dose for 7.2 ± 5.0 days | AZM for 6.8 ± 4.4 days | 61.46 | 61.8 | 61.2 | 66.1 | NR | NR | NR | NR | −45.9 | −37.8 | 22 |
| Cecchini 2017 [41] | Retrospective observational study | France | Multicenter, ICU | 43 | 45 | LVX, OFX, CIP | ERY, RXM, AZM, SPM | NR | NR | 73 | NR | NR | NR | NR | NR | 43 (100) | 45 (100) | 23 |
| Garcia-Vidal 2017 [42] | Retrospective observational study | Spain | Multicenter | 175 | 235 | LVX, 500 mg q.d. for 3 days (IQR, 2–5.25) | AZM (177) 500 mg q.d., for 4 days (IQR, 3–6); CLR (58) 500 mg b.i.d. for 5 days (IQR, 3–6.25) | 59.8 | 62.2 | 69.1 | 74.5 | 100 (57.1) | 102 (43.4) | 77 (44) | 91 (38.7) | 27 (15.4) | 20 (8.5) | 22 |
| Kao 2017 [43] | Retrospective observational study | Taiwan | Single-center | 12 | 16 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | 21 |
| Hung 2018 [44] | Retrospective observational study | Taiwan | Single-center | 38 | 11 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | 21 |
Abbreviations: AZM, azithromycin; b.i.d., twice a day; CIP, ciprofloxacin; CLR, clarithromycin; ERY, erythromycin; IQR, interquartile range; LVX, levofloxacin; M, macrolide monotherapy; NR, not reported (data for the presented variables were not reported in the respective studies); OFX, ofloxacin; PAZ, pazufloxacin; PEF, pefloxacin; q.d., once a day; q.i.d., four times a day; q6h, q8h, q12h, every 6, 8 or 12 hours respectively; Q, fluoroquinolone monotherapy; RXM, roxithromycin; SPM, spiramycin; SPX, sparfloxacin; TVA, trovafloxacin.