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Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Comparing antibiotic treatment for leptospirosis using network meta-analysis: a tutorial

Authors: Cho Naing, Simon A. Reid, Kyan Aung

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

Network meta-analysis consists of simultaneous analysis of both direct comparisons of interventions within randomized controlled trials and indirect comparisons across trials based on a common comparator. In this paper, we aimed to characterise the conceptual understanding and the rationale for the use of network meta-analysis in assessing drug efficacy.

Methods

We selected randomized controlled trials, assessing efficacy of antibiotics for the treatment of leptospirosis as a case study. A pairwise meta-analysis was conducted using a random effect model, assuming that different studies assessed different but related treatment effects. The analysis was then extended to a network meta-analysis, which consists of direct and indirect evidence in a network of antibiotics trials, using a suite of multivariate meta-analysis routines of STATA (mvmeta command). We also assessed an assumption of ‘consistency’ that estimates of treatment effects from direct and indirect evidence are in agreement.

Results

Seven randomised controlled trials were identified for this analysis. These RCTs assessed the efficacy of antibiotics such as penicillin, doxycycline and cephalosporin for the treatment of human leptospirosis. These studies made comparisons between antibiotics (i.e. an antibiotic versus alternative antibiotic) in the primary study and a placebo, except for cephalosporin. These studies were sufficient to allow the creation of a network for the network meta-analysis; a closed loop in which three comparator antibiotics were connected to each other through a polygon. The comparison of penicillin versus the placebo has the largest contribution to the entire network (31.8%). The assessment of rank probabilities indicated that penicillin presented the greatest likelihood of improving efficacy among the evaluated antibiotics for treating leptospirosis.

Conclusions

Findings suggest that network meta-analysis, a meta-analysis comparing multiple treatments, is feasible and should be considered as better precision of effect estimates for decisions when several antibiotic options are available for the treatment of leptospirosis.
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Literature
1.
go back to reference Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.CrossRefPubMedPubMedCentral Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.CrossRefPubMedPubMedCentral
2.
go back to reference Suputtamongkol Y, Niwattayakul K, Suttinont C, Losuwanaluk K, Limpaiboon R, Chierakul W, et al. An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin Infect Dis. 2004;39:1417–24.CrossRefPubMed Suputtamongkol Y, Niwattayakul K, Suttinont C, Losuwanaluk K, Limpaiboon R, Chierakul W, et al. An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin Infect Dis. 2004;39:1417–24.CrossRefPubMed
3.
4.
go back to reference Smith CT, Marson AG, Chadwick DW, Williamson PR. Multiple treatment comparisons in epilepsy monotherapy trials. Trials. 2007;8:34.CrossRef Smith CT, Marson AG, Chadwick DW, Williamson PR. Multiple treatment comparisons in epilepsy monotherapy trials. Trials. 2007;8:34.CrossRef
5.
go back to reference Higgins JP, Whitehead A. Borrowing strength from external trials in a meta-analysis. Stat Med. 1996;15:2733–49.CrossRefPubMed Higgins JP, Whitehead A. Borrowing strength from external trials in a meta-analysis. Stat Med. 1996;15:2733–49.CrossRefPubMed
6.
go back to reference Glenny AM, Altman DG, Song F, Sakarovitch C, Deeks JJ, D’Amico R, et al. Indirect comparisons of competing interventions. Health Technol Assess. 2005;9:1–134.CrossRefPubMed Glenny AM, Altman DG, Song F, Sakarovitch C, Deeks JJ, D’Amico R, et al. Indirect comparisons of competing interventions. Health Technol Assess. 2005;9:1–134.CrossRefPubMed
7.
go back to reference Li T, Puhan MA, Vedula SS, Singh S, Dickersin K. Network meta-analysis-highly attractive but more methodological research is needed. BMC Med. 2011;9:1.CrossRef Li T, Puhan MA, Vedula SS, Singh S, Dickersin K. Network meta-analysis-highly attractive but more methodological research is needed. BMC Med. 2011;9:1.CrossRef
8.
go back to reference Kirkham JJ, Riley RD, Williamson PR. A multivariate meta-analysis approach for reducing the impact of outcome reporting bias in systematic reviews. Stat Med. 2012;31:2179–95.CrossRefPubMed Kirkham JJ, Riley RD, Williamson PR. A multivariate meta-analysis approach for reducing the impact of outcome reporting bias in systematic reviews. Stat Med. 2012;31:2179–95.CrossRefPubMed
9.
go back to reference Torgerson PR, Hagan JE, Costa F, Calcagno J, Kane M, Martinez-Silveira MS, et al. Global burden of leptospirosis: estimated in terms of disability adjusted life years. Plos Negl Trop Dis. 2015;9:e0004122.CrossRefPubMedPubMedCentral Torgerson PR, Hagan JE, Costa F, Calcagno J, Kane M, Martinez-Silveira MS, et al. Global burden of leptospirosis: estimated in terms of disability adjusted life years. Plos Negl Trop Dis. 2015;9:e0004122.CrossRefPubMedPubMedCentral
10.
go back to reference Goris MGA, Kikken V, Straetemans M, Alba S, Goeijenbier M, van Gorp ECM, et al. Towards the burden of human leptospirosis: duration of acute illness and occurrence of post-leptospirosis symptoms of patients in the Netherlands. Plos One. 2013;8:e76549.CrossRefPubMedPubMedCentral Goris MGA, Kikken V, Straetemans M, Alba S, Goeijenbier M, van Gorp ECM, et al. Towards the burden of human leptospirosis: duration of acute illness and occurrence of post-leptospirosis symptoms of patients in the Netherlands. Plos One. 2013;8:e76549.CrossRefPubMedPubMedCentral
11.
go back to reference Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380:2095–128.CrossRefPubMed Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380:2095–128.CrossRefPubMed
12.
go back to reference Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, et al. Global morbidity and mortality of leptospirosis: a systematic review. PLoS Negl Trop Dis. 2015;9:e0003898.CrossRefPubMedPubMedCentral Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, et al. Global morbidity and mortality of leptospirosis: a systematic review. PLoS Negl Trop Dis. 2015;9:e0003898.CrossRefPubMedPubMedCentral
14.
go back to reference Raptis L, Pappas G, Akritidis N. Use of ceftriaxone in patients with severe leptospirosis. Int J Antimicrob Agents. 2006;28:259–61.CrossRefPubMed Raptis L, Pappas G, Akritidis N. Use of ceftriaxone in patients with severe leptospirosis. Int J Antimicrob Agents. 2006;28:259–61.CrossRefPubMed
15.
go back to reference Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: http://handbook.cochrane.org. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: http://​handbook.​cochrane.​org.
17.
go back to reference Jansen JP, Fleurence R, Devine B, Itzler R, Barrett A, Hawkins N, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1. Value Health. 2011;14:429–37.CrossRefPubMed Jansen JP, Fleurence R, Devine B, Itzler R, Barrett A, Hawkins N, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1. Value Health. 2011;14:429–37.CrossRefPubMed
18.
go back to reference Cope S, Zhang J, Saletan S, Smiechowski B, Jansen JP, Schmid P. A process for assessing the feasibility of a network meta-analysis: a case study of everolimusin combination with hormonal therapy versus chemotherapy for advanced breast cancer. BMC Med. 2014;12:1.CrossRef Cope S, Zhang J, Saletan S, Smiechowski B, Jansen JP, Schmid P. A process for assessing the feasibility of a network meta-analysis: a case study of everolimusin combination with hormonal therapy versus chemotherapy for advanced breast cancer. BMC Med. 2014;12:1.CrossRef
19.
go back to reference White IR, Barrett JK, Jackson D, Higgins JPT. Consistency and inconsistency in network meta-analysis: model estimation using multivariate meta-regression. Res Synth Methods. 2012;3:111–25.CrossRefPubMedPubMedCentral White IR, Barrett JK, Jackson D, Higgins JPT. Consistency and inconsistency in network meta-analysis: model estimation using multivariate meta-regression. Res Synth Methods. 2012;3:111–25.CrossRefPubMedPubMedCentral
20.
21.
go back to reference White IR. Multivariate random-effects meta-regression: updates to mvmeta. STATA J. 2011;11:255–70. White IR. Multivariate random-effects meta-regression: updates to mvmeta. STATA J. 2011;11:255–70.
22.
go back to reference Edwards CN, Nicholson GD, Hassell TA, Everard CO, Callender J. Penicillin therapy in icteric leptospirosis. Am J Trop Med Hyg. 1988;39:388–90.PubMed Edwards CN, Nicholson GD, Hassell TA, Everard CO, Callender J. Penicillin therapy in icteric leptospirosis. Am J Trop Med Hyg. 1988;39:388–90.PubMed
23.
go back to reference Watt G, Padre LP, Tuazon ML, Calubaquib C, Santiago E, et al. Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis. Lancet. 1988;1:433–5.CrossRefPubMed Watt G, Padre LP, Tuazon ML, Calubaquib C, Santiago E, et al. Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis. Lancet. 1988;1:433–5.CrossRefPubMed
24.
go back to reference Daher EF, Nogueira CB. Evaluation of penicillin therapy in patients with leptospirosis and acute renal failure. Rev Inst Med Trop Sao Paulo. 2000;42:327–32.CrossRefPubMed Daher EF, Nogueira CB. Evaluation of penicillin therapy in patients with leptospirosis and acute renal failure. Rev Inst Med Trop Sao Paulo. 2000;42:327–32.CrossRefPubMed
25.
go back to reference Costa E, Lopes AA, Sacramento E, Costa YA, Matos ED, Lopes MB, et al. Penicillin at the late stage of leptospirosis: A randomized controlled trial. Rev Inst Med Trop Sao Paulo. 2003;45:141–5.CrossRefPubMed Costa E, Lopes AA, Sacramento E, Costa YA, Matos ED, Lopes MB, et al. Penicillin at the late stage of leptospirosis: A randomized controlled trial. Rev Inst Med Trop Sao Paulo. 2003;45:141–5.CrossRefPubMed
26.
go back to reference Panaphut T, Domrongkitchaiporn S, Vibhagool A, Thinkamrop B, Susaengrat W. Ceftriaxone compared with sodium penicillin g for treatment of severe leptospirosis. Clin Infect Dis. 2003;36:1507–13.CrossRefPubMed Panaphut T, Domrongkitchaiporn S, Vibhagool A, Thinkamrop B, Susaengrat W. Ceftriaxone compared with sodium penicillin g for treatment of severe leptospirosis. Clin Infect Dis. 2003;36:1507–13.CrossRefPubMed
27.
go back to reference McClain JB, Ballou WR, Harrison SM, Steinweg DL. Doxycycline therapy for leptospirosis. Ann Intern Med. 1984;100:696–8.CrossRefPubMed McClain JB, Ballou WR, Harrison SM, Steinweg DL. Doxycycline therapy for leptospirosis. Ann Intern Med. 1984;100:696–8.CrossRefPubMed
28.
go back to reference World Health Organization. Human leptospirosis: guidance for diagnosis, surveillance and control. Geneva: World Health Organization; 2003. World Health Organization. Human leptospirosis: guidance for diagnosis, surveillance and control. Geneva: World Health Organization; 2003.
29.
go back to reference The Malaysian, Ministry of Health. Guidelines for the diagnosis, management, prevention and control of leptospirosis in Malaysia. 1st ed. 2011. The Malaysian, Ministry of Health. Guidelines for the diagnosis, management, prevention and control of leptospirosis in Malaysia. 1st ed. 2011.
30.
go back to reference Guidugli F, Castro AA, Atallah AN. Antibiotics for treating leptospirosis. Cochrane Database Syst Rev. 2000;2:CD001306. Guidugli F, Castro AA, Atallah AN. Antibiotics for treating leptospirosis. Cochrane Database Syst Rev. 2000;2:CD001306.
31.
go back to reference Charan J, Saxena D, Mulla S, Yadav P. Antibiotics for the treatment of leptospirosis: systematic review and meta-analysis of controlled trials. Int J Prev Med. 2013;4:501–10.PubMedPubMedCentral Charan J, Saxena D, Mulla S, Yadav P. Antibiotics for the treatment of leptospirosis: systematic review and meta-analysis of controlled trials. Int J Prev Med. 2013;4:501–10.PubMedPubMedCentral
33.
go back to reference Emmanouilides CE, Kohn OF, Garibaldi R. Leptospirosis complicated by a Jarisch-Herxheimer reaction and adult respiratory distress syndrome: case report. Clin Infect Dis. 1994;18:1004–6.CrossRefPubMed Emmanouilides CE, Kohn OF, Garibaldi R. Leptospirosis complicated by a Jarisch-Herxheimer reaction and adult respiratory distress syndrome: case report. Clin Infect Dis. 1994;18:1004–6.CrossRefPubMed
34.
go back to reference Ghooi RB, Thatte SM. Inhibition of cell wall synthesis--is this the mechanism of action of penicillins? Med Hypotheses. 1995;44:127–31.CrossRefPubMed Ghooi RB, Thatte SM. Inhibition of cell wall synthesis--is this the mechanism of action of penicillins? Med Hypotheses. 1995;44:127–31.CrossRefPubMed
35.
go back to reference Cipriani A, Santilli C, Furukawa TA, Signoretti A, Nakagawa A, McGuire H, Churchill R, Barbui C. Escitalopram versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2009;15(2):CD006532. Cipriani A, Santilli C, Furukawa TA, Signoretti A, Nakagawa A, McGuire H, Churchill R, Barbui C. Escitalopram versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2009;15(2):CD006532.
Metadata
Title
Comparing antibiotic treatment for leptospirosis using network meta-analysis: a tutorial
Authors
Cho Naing
Simon A. Reid
Kyan Aung
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-2145-3

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