Review Article

Comparing Several Treatments with Antibiotics for Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background: We aimed to review relevant randomized controlled trials to assess the relative clinical effects of antibiotic treatment of patients with community-acquired pneumonia (CAP).

Methods: In this meta-analysis, we identified relevant studies from PubMed, Cochrane, and Embase using appropriate keywords. Key pertinent sources in the literature were also reviewed and all articles published through Oct 2019 were considered for inclusion. For each study, we assessed the risk ratios (RRs) or mean difference combined with the 95% confidence interval (CI) to assess and synthesize outcomes.

Results: Overall, 36 studies were consistent with the meta-analysis, involving 17,076 patients. There was no significant difference in the mortality after subgroup analysis: individualized treatment vs. standard treatment; β-lactams plus macrolides vs. β-lactam and/or fluoroquinolone; ceftaroline fosamil vs. ceftriaxone; combination therapy vs. monotherapy or high-dose vs. low-dose. The drug-related adverse event incidence was significantly higher in the ceftriaxone group than in the other drug groups (P<0.05) and also higher in the tigecyline group than in the levofloxacin group (P<0.05). Compared with ceftriaxone, ceftaroline fosamil significantly increased the clinical cure rate at the test-of-cure (TOC) visit in the clinically evaluable population, modified intent-to-treat efficacy (MITTE) population, microbiologically evaluable (ME) population and the microbiological MITTE (mMITTE) population (all P<0.05). Compared with ceftriaxone, ceftaroline fosamil significantly increased the clinical cure rate at the TOC visit in the mMITTE population of Gram positive-Streptococcus pneumoniae (P<0.05) and multidrug-resistant S. pneumoniae (P<0.05).

Conclusion: There was a limited number of included studies in the subgroup analysis, but it will still be necessary to conduct more high-quality randomized controlled trials to confirm the clinical efficacy of different antibiotics used to treat CAP.

1. Ho J, Ip M (2019). Antibiotic-Resistant Community-Acquired Bacterial Pneumonia. Infect Dis Clin North Am, 33(4):1087-103.
2. Voiriot G, Philippot Q, Elabbadi A, et al (2019). Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients. J Clin Med, 8(6):786.
3. Esposito S, Principi N (2019). Defining the aetiology of paediatric community-acquired pneumonia: an unsolved problem. Expert Rev Respir Med, 13(2):153-61.
4. Nascimento-Carvalho AC, Nascimento-Carvalho CM (2019). Clinical management of community-acquired pneumonia in young children. Expert Opin Pharmacother, 20(4):435-42.
5. Welte T, Kantecki M, Stone G, Hammond J (2019). Ceftaroline fosamil as a potential treatment option for Staphylococcus aureus community-acquired pneumonia in adults. Int J Antimicrob Agents, 54(4):410-22.
6. Eljaaly K, Wali H, Basilim A, Alharbi A, Asfour HZ (2019). Clinical cure with ceftriaxone versus ceftaroline or ceftobiprole in the treatment of staphylococcal pneumonia: a systematic review and meta-analysis. Int J Antimicrob Agents, 54(2):149-53.
7. Tansarli GS, Mylonakis E (2018). Systematic Review and Meta-analysis of the Efficacy of Short-Course Antibiotic Treatments for Community-Acquired Pneumonia in Adults. Antimicrob Agents Chemother, 62(9): e00635-18.
8. Wan Y-D, Sun T-W, Liu Z-Q, et al (2016). Efficacy and Safety of Corticosteroids for Community-Acquired Pneumonia. Chest, 149(1):209-19.
9. Huang J, Guo J, Li H, et al (2019). Efficacy and safety of adjunctive corticosteroids therapy for patients with severe community-acquired pneumonia: A systematic review and meta-analysis. Medicine (Baltimore), 98(13):e14636.
10. Bi J, Yang J, Wang Y, et al (2016). Efficacy and Safety of Adjunctive Corticosteroids Therapy for Severe Community-Acquired Pneumonia in Adults: An Updated Systematic Review and Meta-Analysis. PLoS One, 11(11):e0165942.
11. Aliberti S, Ramirez J, Giuliani F, et al (2017). Individualizing duration of antibiotic therapy in community-acquired pneumonia. Pulm Pharmacol Ther, 45:191-201.
12. Bergallo C, Jasovich A, Teglia O, et al (2009). Safety and efficacy of intravenous tigecycline in treatment of community-acquired pneumonia: results from a double-blind randomized phase 3 comparison study with levofloxacin. Diagn Microbiol Infect Dis, 63(1):52-61.
13. Ceccato A, Cilloniz C, Ranzani OT, et al (2017). Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: A post-hoc exploratory analysis of a randomized controlled trial. PLoS One, 12(6):e0178022.
14. Drehobl M, De Salvo M, Lewis D, Breen J (2005). Single-dose azithromycin microspheres vs clarithromycin extended release for the treatment of mild-to-moderate community-acquired pneumonia in adults. Chest, 128(4):2230-7.
15. el Moussaoui R, de Borgie C, van den Broek P, et al (2006). Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study. BMJ, 332(7554):1355.
16. English M, Fredericks C, Milanesio N, et al (2012). Cethromycin versus clarithromycin for community-acquired pneumonia: comparative efficacy and safety outcomes from two double-blinded, randomized, parallel-group, multicenter, multinational noninferiority studies. Antimicrob Agents Chemother, 56(4):2037-47.
17. File TM, Jr., Low DE, Eckburg PB, et al (2010). Integrated Analysis of FOCUS 1 and FOCUS 2: Randomized, Doubled‐Blinded, Multicenter Phase 3 Trials of the Efficacy and Safety of Ceftaroline Fosamil versus Ceftriaxone in Patients with Community‐Acquired Pneumonia. Clin Infect Dis, 51(12):1395-405.
18. File TM, Jr., Low DE, Eckburg PB, et al (2011). FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother, 66 Suppl 3:iii19-32.
19. File TM, Mandell LA, Tillotson G, et al (2007). Gemifloxacin once daily for 5 d versus 7 d for the treatment of community-acquired pneumonia: a randomized, multicentre, double-blind study. J Antimicrob Chemother, 60(1):112-20.
20. File TM, Jr., Segreti J, Dunbar L, et al (1997). A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother, 41(9):1965-72.
21. Fujita J, Niki Y, Kadota J, et al (2013). Clinical and bacteriological efficacies of sitafloxacin against community-acquired pneumonia caused by Streptococcus pneumoniae: nested cohort within a multicenter clinical trial. J Infect Chemother, 19(3):472-9.
22. Garin N, Genné D, Carballo S, et al (2014). β-Lactam Monotherapy vs β-Lactam–Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia. JAMA Intern Med, 174(12):1894-901.
23. Jandourek A, Smith A, Llorens L, et al (2014). Efficacy of ceftaroline fosamil for bacteremia associated with community-acquired bacterial pneumonia. Hosp Pract (1995), 42(1):75-8.
24. Kohno S, Yanagihara K, Yamamoto Y, et al (2013). Early switch therapy from intravenous sulbactam/ampicillin to oral garenoxacin in patients with community-acquired pneumonia: a multicenter, randomized study in Japan. J Infect Chemother, 19(6):1035-41.
25. Kuzman I, Ðaković-Rode O, Oremuš M, Banaszak AM (2005). Clinical Efficacy and Safety of a Short Regimen of Azithromycin Sequential Therapy vs Standard Cefuroxime Sequential Therapy in the Treatment of Community-Acquired Pneumonia: An International, Randomized, Open-Label Study. J Chemother, 17(6):636-42.
26. Leroy O, Saux P, Bédos J, Caulin E (2005). Comparison of levofloxacin (L) and cefotaxime (C) combined with ofloxacin (O) for treatment of severe community-acquired pneumonia (CAP) in the intensive care unit. Crit Care, 8(Supplement 1):230.
27. Liu Y, Zhang Y, Wu J, et al (2017). A randomized, double-blind, multicenter phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia. J Microbiol Immunol Infect, 50(6):811-20.
28. Lode H, Magyar P, Muir J, et al (2004). Once-daily oral gatifloxacin vs three-times-daily co-amoxiclav in the treatment of patients with community-acquired pneumonia. Clin Microbiol Infect, 10(6):512-20.
29. Low DE, File TM, Jr., Eckburg PB, et al (2011). FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother, 66 Suppl 3:iii33-44.
30. Manu C, G. AS, A. MM (2018). Comparative efficacy and safety analysis of CSE-1034: An open labeled phase III study in community acquired pneumonia. J Infect Public Health, 11(5):691-7.
31. Nicholson SC, Welte T, Jr TMF, et al (2012). A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation. Int J Antimicrob Agents, 39(3):240-6.
32. Oosterheert J, Bonten M, Schneider M, et al. (2006). Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial. BMJ, 333(7580):1193.
33. Paris R, Confalonieri M, Dal Negro R, et al (2008). Efficacy and Safety of Azithromycin 1 g Once Daily for 3 Days in the Treatment of Community-Acquired Pneumonia: an Open-Label Randomised Comparison with Amoxicillin-Clavulanate 875/125 mg Twice Daily for 7 Days. J Chemother, 20(1):77-86.
34. Pertel P, Bernardo P, Fogarty C, et al (2008). Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin Infect Dis, 46(8):1142-51.
35. Postma DF, van Werkhoven CH, van Elden LJR, et al (2015). Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults. N Engl J Med, 372(14):1312-23.
36. Rank DR, Friedland HD, Laudano JB (2011). Integrated safety summary of FOCUS 1 and FOCUS 2 trials: Phase III randomized, double-blind studies evaluating ceftaroline fosamil for the treatment of patients with community-acquired pneumonia. J Antimicrob Chemother, 66 Suppl 3:iii53-9.
37. Shorr AF, Khashab MM, Xiang JX, et al (2006). Levofloxacin 750-mg for 5 days for the treatment of hospitalized Fine Risk Class III/IV community-acquired pneumonia patients. Respir Med, 100(12):2129-36.
38. Tanaseanu C, Milutinovic S, Calistru P, et al (2009). Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia. BMC Pulm Med, 9:44.
39. Torres A, Garau J, Arvis P, et al (2008). Moxifloxacin monotherapy is effective in hospitalized patients with community-acquired pneumonia: the MOTIV study--a randomized clinical trial. Clin Infect Dis, 46(10):1499-509.
40. Uranga A, España P, Bilbao A, et al (2016). Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial. JAMA Intern Med, 176(9):1257-65.
41. van Rensburg D, Perng R, Mitha I, et al (2010). Efficacy and safety of nemonoxacin versus levofloxacin for community-acquired pneumonia. Antimicrob Agents Chemother, 54(10):4098-106.
42. Welte T, Petermann W, Schurmann D, et al (2005). Treatment with Sequential Intravenous or Oral Moxifloxacin Was Associated with Faster Clinical Improvement than Was Standard Therapy for Hospitalized Patients with Community-Acquired Pneumonia Who Received Initial Parenteral Therapy. Clin Infect Dis, 41(12):1697-705.
43. Yanagihara K, Fukuda Y, Seki M, et al (2006). Clinical Comparative Study of Sulbactam/Ampicillin and Imipenem/Cilastatin in Elderly Patients with Community-Acquired Pneumonia. Intern Med, 45(17):995-9.
44. Zhao X, Wu J, Xiu Q, et al (2014). A randomized controlled clinical trial of levofloxacin 750 mg versus 500 mg intravenous infusion in the treatment of community-acquired pneumonia. Diagn Microbiol Infect Dis, 80(2):141-7.
45. Zhong NS, Sun T, Zhuo C, et al (2015). Ceftaroline fosamil versus ceftriaxone for the treatment of Asian patients with community-acquired pneumonia: a randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial. Lancet Infect Dis, 15(2):161-71.
46. Lin TY, Lin SM, Chen HC, et al (2007). An open-label, randomized comparison of levofloxacin and amoxicillin/clavulanate plus clarithromycin for the treatment of hospitalized patients with community-acquired pneumonia. Chang Gung Med J, 30(4):321-32.
Files
IssueVol 50 No 6 (2021) QRcode
SectionReview Article(s)
Published2021-06-10
Keywords
Antibiotic Community-acquired pneumonia Meta-analysis β-lactams Macrolides

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Bai F, Li X. Comparing Several Treatments with Antibiotics for Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Iran J Public Health. 50(6):1108-1119.