Respiratory Fluoroquinolones Monotherapy versus <i>β</i>-lactams plus Macrolides Combination Therapy for Non-ICU Hospitalized Community-acquired Pneumonia Patients:A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 FANHong ¹ , LIUSi-tong ¹ , TONGXiang ¹ , PENGShi-feng ¹ , MAYao ² , YANZhi-peng ¹ , YANGXin ¹ ,  DULiang ³

1. Department of Respiratory Medicine and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China;
2. Department of Geriatric Medicine, No.;
3. West China Teaching Hospital, Sichuan University, Chengdu 610041, China;
1. The Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

DULiang, Email: duliang0606@vip.sina.com

Keywords：

Community-acquired pneumonia; Fluoroquinolones; β-Lactams; Macrolides; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20150137

Video：

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Objective To systematically review the efficacy and safety of respiratory fluoroquinolones monotherapy versus β-lactams plus macrolides combination therapy for non-ICU hospitalized community acquired pneumonia (CAP) patients. Methods We searched databases including PubMed, the Cochrane Library (Issue 3, 2015), EMbase, CNKI, WanFang Data, VIP and CBM to identify randomized controlled trials (RCTs) involving the comparison of fluoroquinolones monotherapy with β-lactams plus macrolides combination treatment for the non-ICU hospitalized patients with CAP up to April 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed the risk bias of included studies, and then meta-analysis was performed using the RevMan 5.0 software. Results A total of 17 RCTs involving 5 423 patients were included. The results of meta-analysis showed that there was no significant difference between the two therapy groups on the mortality. For the clinical treatment success rates, no significant differences between the two groups were found based on the data of intention-to-treat (ITT) and per-protocol (PP) analyses. However, respiratory fluoroquinolones monotherapy was associated with higher clinical treatment success rates based on the data that it was unclear whether ITT or PP analysis was used (RR=1.08, 95% CI 1.01 to 1.18, P=0.02), especially in Asians (RR=1.10, 95%CI 1.02 to 1.18, P=0.01). Additionally, respiratory fluoroquinolones monotherapy was associated with less adverse events (RR=0.81, 95%CI 0.73 to 0.90, P<0.000 1), especially in Caucasians (RR=0.64, 95%CI 0.36 to 1.14, P=0.13). Conclusion Current evidence shows that the efficacy of respiratory fluoroquinolones monotherapy may be similar to β-lactams plus macrolides combination treatment for non-ICU hospitalized CAP patients. Since the limitation of quantity and quality of included studies, large-scale high-quality RCTs are needed to verify the above conclusion.

Citation： FANHong, LIUSi-tong, TONGXiang, PENGShi-feng, MAYao, YANZhi-peng, YANGXin, DULiang. Respiratory Fluoroquinolones Monotherapy versus β-lactams plus Macrolides Combination Therapy for Non-ICU Hospitalized Community-acquired Pneumonia Patients:A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(7): 824-832. doi: 10.7507/1672-2531.20150137 Copy

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2.	Musher DM,Thorner AR.Community-acquired pneumonia.N Engl J Med,2014,371(17):1619-1628.
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14.	Erard V,Lamy O,Bochud PY,et al.Full-course oral levofloxacin for treatment of hospitalized patients with community-acquired pneumonia.Eur J Clin Microbiol Infect Dis,2004,23(2):82-88.
15.	Finch R,Schürmann D,Collins O,et al.Randomized controlled trial of sequential intravenous (iv) and oral moxifloxacin compared with sequential iv and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment.Antimicrob Agents Chemother,2002,46(6):1746-1754.
16.	Fogarty C,Siami G,Kohler R,et al.Multicenter,open-label,randomized study to compare the safety and efficacy of levofloxacin versus ceftriaxone sodium and erythromycin followed by clarithromycin and amoxicillin-clavulanate in the treatment of serious community-acquired pneumonia in adults.Clin Infect Dis,2004,38(Suppl 1):S16-S23.
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21.	Lode H,File TM,Mandell L,et al.Oral gemifloxacin versus sequential therapy with intravenous ceftriaxone/oral cefuroxime with or without a macrolide in the treatment of patients hospitalized with community-acquired pneumonia:a randomized,open-label,multicenter study of clinical efficacy and tolerability.Clin Ther,2002,24(11):1915-1936.
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25.	Welte T,Petermann W,Schürmann D,et al.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,2005,41(12):1697-1705.
26.	Xu S,Xiong S,Xu Y,et al.Efficacy and safety of intravenous moxifloxacin versus cefoperazone with azithromycin in the treatment of community acquired pneumonia.J Huazhong Univ Sci Technolog Med Sci,2006,26(4):421-424.
27.	杨淑桂,张山红.盐酸莫西沙星与头孢曲松钠联合阿奇霉素治疗中重度老年社区获得性肺炎的疗效与成本-效果分析.中国新药杂志,2009,18(10):962-964.
28.	Zervos M,Mandell LA,Vrooman PS,et al.Comparative efficacies and tolerabilities of intravenous azithromycin plus ceftriaxone and intravenous levofloxacin with step-down oral therapy for hospitalized patients with moderate to severe community-acquired pneumonia.Treat Respir Med,2004,3(5):329-336.
29.	黄刚,蒋一雅,周燕娟,等.莫西沙星序贯治疗老年社区获得性肺炎临床研究.南京医科大学学报:自然科学版,2008,28(11):1457-1460.
30.	Guidance for Industry-Draft.Developing Antimicrobial Drugs-General Considerations for Clinical Trials.July 1998.Available at:http://www.fda.govlcderlguidancei2580dft.pdf.
31.	Skalsky K,Yahav D,Lador A,et al.Macrolides vs.quinolones for community-acquired pneumonia:meta-analysis of randomized controlled trials.Clin Microbiol Infect,2013,19(4):370-378.

1. 中华医学会呼吸病学分会.社区获得性肺炎诊断和治疗指南.中华结核和呼吸杂志,2006,29(10):651-655.
2. Musher DM,Thorner AR.Community-acquired pneumonia.N Engl J Med,2014,371(17):1619-1628.
3. Mandell LA,Wunderink RG,Anzueto A,et al.Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.Clin Infect Dis,2007,44(Suppl 2):S27-72.
4. Lim WS,Baudouin SV,George RC,et al.BTS guidelines for the management of community acquired pneumonia in adults:update 2009.Thorax,2009,64(Suppl 3):iii1-55.
5. Woodhead M,Blasi F,Ewig S,et al.Guidelines for the management of adult lower respiratory tract infections--full version.Clin Microbiol Infect,2011,17(Suppl 6):E1-59.
6. 韩彬,宁学聪,柴文戍.莫西沙星与头孢曲松联合阿奇霉素治疗社区获得性肺炎的临床疗效.中国药房,2010(36):3400-3401.
7. 吴红芝,李晓辕,左孟华,等.莫西沙星治疗老年社区获得性肺炎的疗效.中国老年学杂志,2013,33(6):2923-2924.
8. 曹婕,陈君君,周华,等.经验性治疗社区获得性肺炎中的疗效评价.中国微生态学杂志,2012,24(10):904-906.
9. Vardakas KZ,Siempos Ⅱ,Grammatikos A,et al.Respiratory fluoroquinolones for the treatment of community-acquired pneumonia:a meta-analysis of randomized controlled trials.CMAJ,2008,179(12):1269-1277.
10. Asadi L,Sligl WI,Eurich DT,et al.Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia:a systematic review and meta-analysis.Clin Infect Dis,2012,55(3):371-380.
11. Salkind AR,Cuddy PG,Foxworth JW.Fluoroquinolone treatment of community-acquired pneumonia:a meta-analysis.Ann Pharmacother,2002,36(12):1938-1943.
12. An MM,Zou Z,Shen H,et al.Moxifloxacin monotherapy versus β-lactam-based standard therapy for community-acquired pneumonia:a meta-analysis of randomised controlled trials.Int J Antimicrob Agents,2010,36(1):58-65.
13. Higgins J,Altman D.Chapter 8:Assessing risk of bias in included studies.Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0(updated March 2011).The Cochrane Collaboration,2011.Available at:www.cochrane-handbook.org.
14. Erard V,Lamy O,Bochud PY,et al.Full-course oral levofloxacin for treatment of hospitalized patients with community-acquired pneumonia.Eur J Clin Microbiol Infect Dis,2004,23(2):82-88.
15. Finch R,Schürmann D,Collins O,et al.Randomized controlled trial of sequential intravenous (iv) and oral moxifloxacin compared with sequential iv and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment.Antimicrob Agents Chemother,2002,46(6):1746-1754.
16. Fogarty C,Siami G,Kohler R,et al.Multicenter,open-label,randomized study to compare the safety and efficacy of levofloxacin versus ceftriaxone sodium and erythromycin followed by clarithromycin and amoxicillin-clavulanate in the treatment of serious community-acquired pneumonia in adults.Clin Infect Dis,2004,38(Suppl 1):S16-S23.
17. Frank E,Liu J,Kinasewitz G,et al.A multicenter,open-label,randomized comparison of levofloxacin and azithromycin plus ceftriaxone in hospitalized adults with moderate to severe community-acquired pneumonia.Clin Ther,2002,24(8):1292-1308.
18. 高微华,吴开松,林宇辉,等.莫西沙星与头孢呋辛联用阿奇霉素治疗社区获得性肺炎的对照研究.中华医院感染学杂志,2009,19(22):3105-3107.
19. Katz E,Larsen LS,Fogarty CM,et al.Safety and efficacy of sequential iv to po moxifloxacin versus conventional combination therapies for the treatment of community-acquired pneumonia in patients requiring initial iv therapy.J Emerg Med,2004,27(4):395-405.
20. Lin T,Lin S,Chen H,et al.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,2007,30(4):321.
21. Lode H,File TM,Mandell L,et al.Oral gemifloxacin versus sequential therapy with intravenous ceftriaxone/oral cefuroxime with or without a macrolide in the treatment of patients hospitalized with community-acquired pneumonia:a randomized,open-label,multicenter study of clinical efficacy and tolerability.Clin Ther,2002,24(11):1915-1936.
22. Portier H,Brambilla C,Garre M,et al.Moxifloxacin monotherapy compared to amoxicillin-clavulanate plus roxithromycin for nonsevere community-acquired pneumonia in adults with risk factors.Eur J Clin Microbiol Infect Dis,2005,24(6):367-376.
23. Postma DF,van Werkhoven CH,van Elden LJ,et al.Antibiotic treatment strategies for community-acquired pneumonia in adults.N Engl J Med,2015,372(14):1312-1323.
24. Torres A,Muir J,Corris P,et al.Effectiveness of oral moxifloxacin in standard first-line therapy in community-acquired pneumonia.Eur Respir J,2003,21(1):135-143.
25. Welte T,Petermann W,Schürmann D,et al.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,2005,41(12):1697-1705.
26. Xu S,Xiong S,Xu Y,et al.Efficacy and safety of intravenous moxifloxacin versus cefoperazone with azithromycin in the treatment of community acquired pneumonia.J Huazhong Univ Sci Technolog Med Sci,2006,26(4):421-424.
27. 杨淑桂,张山红.盐酸莫西沙星与头孢曲松钠联合阿奇霉素治疗中重度老年社区获得性肺炎的疗效与成本-效果分析.中国新药杂志,2009,18(10):962-964.
28. Zervos M,Mandell LA,Vrooman PS,et al.Comparative efficacies and tolerabilities of intravenous azithromycin plus ceftriaxone and intravenous levofloxacin with step-down oral therapy for hospitalized patients with moderate to severe community-acquired pneumonia.Treat Respir Med,2004,3(5):329-336.
29. 黄刚,蒋一雅,周燕娟,等.莫西沙星序贯治疗老年社区获得性肺炎临床研究.南京医科大学学报:自然科学版,2008,28(11):1457-1460.
30. Guidance for Industry-Draft.Developing Antimicrobial Drugs-General Considerations for Clinical Trials.July 1998.Available at:http://www.fda.govlcderlguidancei2580dft.pdf.
31. Skalsky K,Yahav D,Lador A,et al.Macrolides vs.quinolones for community-acquired pneumonia:meta-analysis of randomized controlled trials.Clin Microbiol Infect,2013,19(4):370-378.

Chinese Journal of Evidence-Based Medicine

Respiratory Fluoroquinolones Monotherapy versus β-lactams plus Macrolides Combination Therapy for Non-ICU Hospitalized Community-acquired Pneumonia Patients:A Meta-analysis

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