Macrolide Therapy in Patients with Sepsis or Septic Shock: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Protocol and Registration
2.2. Inclusion and Exclusion Criteria
2.3. Search Strategy
2.4. Study Selection, Data Extraction
2.5. Quality Assessment and Risk of Bias Evaluation
2.6. Statistical Methods
3. Results
3.1. Study Selection
3.2. Study and Patient’s Characteristics
3.3. Primary Outcome
3.4. Secondary Outcome
3.5. Quality of Included Studies and Certainty of Evidence
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study, Year | Study Design | Site | Total n (Macrolide/Control) | Male, n | Age, Mean ± SD or Median (IQR), Years | Type of Drug | Dose of Macrolide (mg) | Cause of Sepsis | Follow-Up Duration |
---|---|---|---|---|---|---|---|---|---|
Adrie, 2013 [16] | PC | 12 ICUs, France | 635 (164/471) | 411 | 62 (46–76) | NR | NR | Pneumonia | 60 days |
Afshar, 2016 [6] | RC | Single center, USA | 105 (29/76) | 63 | 55.2 ± 16.4 | Azithromycin | NR | All cause | NR |
Behal, 2022 [17] | RC | Single center, USA | 737 (152/585) | 411 | 61 (50–70)/ 56 (45–66) | Azithromycin | NR | All cause | NR |
Giamarellos-Bourboulis, 2008 [8] | RCT | Multicenter, Greece | 200 (100/100) | 147 | 58.4 ± 19.1 | Clarithromycin | 1000 | Pneumonia | 28 days |
Giamarellos-Bourboulis, 2014 [18] | RCT | Multicenter, Greece | 600 (302/298) | 270 | 66.9 ± 19.6 | Clarithromycin | 1000 | All cause | 28 days |
Johnson, 2023 [20] | RC | 3 ICUs, USA | 258 (124/134) | 147 | 62.2 ± 12.8 | Azithromycin | NR | All cause | NR |
Karakike, 2022 [21] | RCT | Multicenter, Greece and Belgium | 110 (55/55) | 72 | 74 (62–80) | Clarithromycin | 1000 | All cause | 90 days |
Kawamura, 2016 [7] | RC | Single center, Japan | 125 (29/96) | 85 | 75 (66–82) | Azithromycin | NR | All cause | 60 days |
Reijnders, 2022 [22] | PC | 2 ICUs, The Netherlands | 705 (235/470) | 447 | 60.9 ± 14.8 | Erythromycin | 120–250 mg (up to 600 mg/d) | All cause | 90 days |
Restrepo, 2009 [23] | RC | 2 ICUs, USA | 237 (104/133) | 189 | 61.3 ± 16.7 | NR | NR | Pneumonia | 90 days |
Trifi, 2024 [24] | RCT | Single center, Tunisia | 110 (55/55) | 70 | 63 (51–78)/64 (54–77) | Erythromycin | 3000 | All cause | 28 days |
Study, Year | Overall Mortality, n (Macrolide/Control) | 28/30-Day Mortality, n (Macrolide/ Control) | 60-Day Mortality, n (Macrolide/ Control) | 90-Day Mortality, n (Macrolide/ Control) | ICU LOS, Mean ± SD or Median (IQR), Days (Macrolide/ Control) | Hospital LOS, Mean ± SD or Median (IQR), Days (Macrolide/ Control) |
---|---|---|---|---|---|---|
Adrie, 2013 [16] | 35/123 | NR | 35/123 | NR | 7 (3.5–15.5)/6 (3–15) | 17.5 (10.5–35)/15 (8–33) |
Afshar, 2016 [6] | 1/13 | 1/13 | NR | NR | NR | 11 (8–14)/13 (8–25) |
Behal, 2022 [17] | 41/189 | NR | NR | NR | 5.8 (2.9–12.1)/5.5 (2.9–11.1) | 10.3 (5.2–18.6)/9.5 (5.1–18.7) |
Giamarellos-Bourboulis, 2008 [8] | 21/24 | 21/24 | NR | NR | 23.4 (±7.1)/21.6 (±8.22) | NR |
Giamarellos-Bourboulis, 2014 [18] | 56/51 | 56/51 | NR | NR | NR | NR |
Johnson, 2023 [20] | 46/51 | NR | NR | NR | 8.4 (4.6–15.6)/8.4 (3.6–17.2) | 13.9 (8.3–24.2)/15.4 (8.1–26.9) |
Karakike, 2022 [21] | 41/38 | 27/25 | NR | 41/38 | NR | NR |
Kawamura, 2016 [7] | 10/48 | NR | 10/48 | NR | NR | NR |
Reijnders, 2022 [22] | 67/74 | 54/56 | NR | 67/74 | 8 (5–13)/8 (5–13) | 22 (12–37.5)/21 (12–39) |
Restrepo, 2009 [23] | 13/45 | 11/37 | NR | 13/45 | NR | 10.6 (±10.1)/9.2 (±9.5) |
Trifi, 2024 [24] | 28/26 | 28/26 | NR | NR | 15 (12–18)/18 (11–28) | NR |
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Kim, K.; Lee, J. Macrolide Therapy in Patients with Sepsis or Septic Shock: A Systematic Review and Meta-Analysis. J. Clin. Med. 2025, 14, 6254. https://doi.org/10.3390/jcm14176254
Kim K, Lee J. Macrolide Therapy in Patients with Sepsis or Septic Shock: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2025; 14(17):6254. https://doi.org/10.3390/jcm14176254
Chicago/Turabian StyleKim, Kyeongdeok, and Jihye Lee. 2025. "Macrolide Therapy in Patients with Sepsis or Septic Shock: A Systematic Review and Meta-Analysis" Journal of Clinical Medicine 14, no. 17: 6254. https://doi.org/10.3390/jcm14176254
APA StyleKim, K., & Lee, J. (2025). Macrolide Therapy in Patients with Sepsis or Septic Shock: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine, 14(17), 6254. https://doi.org/10.3390/jcm14176254