Network meta-analysis of success rate and safety in antibiotic treatments of bronchitis

Figures & data

Table 1 Study and patient characteristics

Study	Size	Blind	Diseases	Age	Drug	Dose and duration
β-Lactams vs placebo
Johnston et al^Citation18	36	Double	Chronic bronchitis	55	Phenethicillin/placebo	250 mg bid (1–6 months)/bid (1–6 months)
Tetracyclines vs placebo
Buchanan et al^Citation13	36	Double	Chronic bronchitis	61.1	Tetracycline/placebo	250 mg bid (1–12 months)/bid (1–12 months)
Stott and West^Citation69	207	–	Cough and purulent sputum	>14	Doxycycline/placebo	Dose NA (1–7 or 14 days)/(1–7 or 14 days)
Verheij et al^Citation56	158	Double	Acute cough with purulent sputum	≥18	Doxycycline/placebo	200 mg (1 day) and 100 mg qd (2–10 days)/qd (1–10 days)
Sulfonamides vs placebo
Davies and Drake^Citation67	218	Double	Chronic bronchitis	55	Sulfamethopyrazine/placebo	2 g once a week (1–5 months)/once a week (1–5 months)
β-Lactams vs macrolides
Aidons^Citation63	125	Double	Chronic bronchitis, AECB	58	Ampicillin/clarithromycin	250 mg qid (1–7 to 14 days)/250 mg bid (1–7 to 14 days)
Bachand^Citation62	225	Double	COPD, AECB	56.1	Ampicillin/clarithromycin	250 mg qid (up to 1–10 days)/250 mg bid (1–10 days)
Guay and Craft^Citation60	103	Single	Chronic bronchitis, AECB	53.9	Ampicillin/clarithromycin	500 mg qid (up to 14 days)/500 mg bid (up to 14 days)
Mertens et al^Citation59	50	Double	Chronic bronchitis, AECB	≥18	Amoxicillin/azithromycin	500 mg tid (1–5 days)/500 mg qd (1–3 days)
Schouenborg et al^Citation45	236	Single	Chronic bronchitis, AECB	61	Pivampicillin/azithromycin	700 mg bid (1–10 days)/500 mg qd (1–3 days)
Zervos et al^Citation2	373	Double	AECB	50.5	Cefuroxime/telithromycin	500 mg bid (1–10 days)/800 mg qd (1–5 days)
β-Lactams vs quinolones
Blasi et al^Citation34	40	Open-label	AECB	65	Cefditoren/levofloxacin	200 mg bid (1–5 days)/500 mg qd (1–7 days)
Chodosh^Citation58	194	Double	Chronic bronchitis, AECB	≥18	Amoxicillin/fleroxacin	500 mg tid (1–7 days)/400 mg qd (1–7 days)
Ulmer^Citation57	623	Double	Chronic bronchitis, AECB	≥18	Amoxicillin/fleroxacin	500 mg tid (1–7 days)/400 mg qd (1–7 days)
Grassi et al^Citation4	470	–	Chronic bronchitis, AECB	69.6	Ceftriaxone/moxifloxacin	1 g qd (1–7 days)/400 mg qd (1–5 days)
Wilson et al^Citation37	272	Open-label	AECB	68.1	Ceftriaxone then cefuroxime/gemifloxacin	1 g qd (1–3 days) then 500 mg bid (up to 7 days)/320 mg qd (1–5 days)
Wilson et al^Citation14	730	Double	Chronic bronchitis, AECB	63.8	Amoxicillin, clarithromycin, or cefuroxime-axetil/moxifloxacin	500 mg tid, 500 mg bid, or 250 mg bid (1–7 days)/400 mg qd (1–5 days)
β-Lactams vs sulfonamides
Gove and Cayton^Citation64	37	Double	AECB	65	Amoxicillin/TMP	250 mg tid (1–7 days)/200 mg bid (1–7 days)
β-Lactams vs double sulfonamides
Leone et al^Citation21	30	–	Chronic bronchitis, AECB	72	Ampicillin/TMP + SDZ	500 mg qid (1–7 days)/150+450 mg bid (1–7 days)
Pines et al^Citation68	100	Single	Chronic bronchitis, AECB	>39	Amoxicillin/TMP+ SMX	500 mg tid (1–10 days)/160+800 mg tid or bid (1–5 months)
Sachs et al^Citation54	71	Double	Chronic bronchitis, AECB	>18	Amoxicillin/TMP+ SMX	500 mg tid (1–7 days)/160+800 mg bid (1–7 days)
Anderson et al^Citation66	39	Double	Chronic bronchitis, AECB	66	Cefaclor/TMP + SMX	500 mg tid (1–7 days)/80+400 mg qd (1–7 days)
Macrolides vs tetracyclines
De Vlieger et al^Citation20	74	Double	Chronic bronchitis, AECB	57.6	Roxithromycin/doxycycline	300 mg qd (1–7 to 14 days)/200 mg qd (1–7 to 14 days)
Macrolides vs quinolones
Chodosh et al^Citation16	855	Double	Chronic bronchitis, AECB	55.5	Clarithromycin/moxifloxacin	500 mg bid (1–10 days)/400 mg qd (1–5 to 10 days)
DeaBate et al^Citation15	513	Double	Chronic bronchitis, AECB	54.5	Azithromycin/moxifloxacin	500 mg qd (1 day) and 250 mg qd (2–5 days)/400 mg qd (1–5 days)
Weiss^Citation40	283	–	Chronic bronchitis, AECB	54	Clarithromycin/levofloxacin	500 mg bid (1–10 days)/500 mg qd (1–10 days)
Wilson et al^Citation48	745	Double	Chronic bronchitis, AECB	60.2	Clarithromycin/moxifloxacin	500 mg bid (1–7 days)/400 mg qd (1–5 days)
Wilson et al^Citation19	709	Double	Chronic bronchitis, AECB	>40	Clarithromycin/gemifloxacin	500 mg bid (1–7 days)/320 mg qd (1–5 days)
Gotfried et al^Citation43	527	Double	AECB	49	Clarithromycin/gatifloxacin	500 mg bid (1–10 days)/400 mg qd (1–5 to 7 days)
Kreis^Citation46	399	–	Chronic bronchitis, AECB	54.7	Azithromycin/moxifloxacin	500 mg qd (1 day) and 250 mg qd (2–5 days)/400 mg qd (1–5 days)
Langan et al^Citation45	802	Double	AECB	56.6	Clarithromycin/grepafloxacin	250 mg bid (1–10 days)/400 mg qd (1–5 to 10 days)
Zervos et al^Citation12	329	–	Chronic bronchitis, AECB	55.5	Azithromycin/moxifloxacin	500 mg qd (1–3 days)/400 mg qd (1–5 days)
Martinez et al^Citation35	394	Double	Chronic bronchitis, AECB	≥18	Azithromycin/levofoxacin	500 mg qd (1 day) and 250 mg qd (2–5 days)/750 mg qd (1–3 days)
Macrolides vs double β-lactams
Aubier et al^Citation42	320	Double	AECB	61.5	Telithromycin/amoxicillin + clavulanate	800 mg qd (1–5 days)/500+125 mg tid (1–10 days)
Zachariah^Citation52	367	Double	Acute bronchitis, AECB	14–93	Azithromycin/amoxicillin + clavulanate	500 mg qd (1–3 days)/37 mg tid (1–10 days)
Anzueto et al^Citation44	283	Single	Chronic bronchitis, AECB	57.2	Clarithromycin/amoxicillin + clavulanate	1,000 mg qd (1–7 days)/875+125 mg bid (1–10 days)
Beghi et al^Citation55	142	Open-label	Chronic bronchitis, AECB	65.9	Azithromycin/amoxicillin + clavulanate	500 mg qd (1–3 days)/875+125 mg bid (1–10 days)
Dautzenberg et al^Citation61	446	Open-label	Chronic bronchitis, AECB	≥18	Roxithromycin/amoxicillin + clavulanate	150 mg bid (1–14 days)/500+125 mg tid (1–14 days)
Gris^Citation53	69	Double	Acute/chronic bronchitis, AECB	≥18	Azithromycin/amoxicillin + clavulanate	500 mg qd (1–3 days)/500+125 mg tid (1–10 days)
Hoepelman et al^Citation51	123	Double	Chronic bronchitis, AECB	≥18	Azithromycin/amoxicillin + clavulanate	500 mg qd (1–3 days)/500+125 mg tid (1–10 days)
Martinot et al^Citation17	243	Single	Chronic bronchitis, AECB	64.4	Clarithromycin/amoxicillin + clavulanate	500 mg qd (1–7 days)/500+125 mg tid (1–7 days)
Van Royen et al^Citation50	334	–	Chronic bronchitis, AECB	62.9	Dirithromycin/amoxicillin + clavulanate	500 mg qd (1–5 days)/500+125 mg tid (1–7 or 10 days)
Quinolones vs double β-lactams
Soler et al^Citation38	405	Double	AECB	61	Gatifloxacin/amoxicillin + clavulanate
File et al^Citation47	600	Double	Chronic bronchitis, AECB	64.2	Gemifloxacin/amoxicillin + clavulanate	320 mg qd h (1–5 days)/500+125 mg tid (1–7 days)
Schaberg et al^Citation4	575	–	Chronic bronchitis, AECB	59.6	Moxifloxacin/amoxicillin + clavulanate	400 mg qd (1–5 days)/500+125 mg bid (1–7 days)
Starakis et al^Citation36	162	Open-label	Chronic bronchitis, AECB	59.6	Moxifloxacin/amoxicillin + clavulanate	400 mg qd (1–5 days)/500+125 mg tid (1–7 days)
Double β-lactams vs double sulfonamides
Lal et al^Citation65	49	–	Chronic bronchitis, AECB	62.6	Pivampicillin + pivmecillinam/TMP+SMX	375+300 mg bid (1–10 days)/240+1,200 mg bid (1–10 days)
β-Lactams vs macrolides vs quinolones
Amsden et al^Citation39	327	Double-blind	Chronic bronchitis, AECB	35–75	Cefuroxime-axetil/azithromycin/levofoxacin	250 mg bid (1–10 days)/500 mg qd (1 day) and 250 mg qd (2–5 days)/500 mg qd (1–7 days)

Abbreviations: AECB, acute bacterial exacerbation of chronic bronchitis; COPD, chronic obstructive pulmonary disease; NA, not applicable; TMP, trimethoprim; SDZ, sulfadiazine; SMX, sulphamethoxazole.

Figure 1 Flow diagram of literature search.

Figure 2 Network meta-analysis results for the endpoints of ITT patient treatment success and CE patient treatment success rates. The network plots show direct comparison of different therapies, with node size corresponding to sample size. The number of included studies for specific direct comparison governs the thickness of solid lines. ORs with 95% CrIs are applied to evaluate the efficacy outcomes. Note that in the upper half of the table, column treatments are compared against row treatments, whereas in the lower half of the table, row treatments are compared against column treatments. Bold data represents significant results.

Abbreviations: ITT, intention-to-treat; CE, clinically evaluable; OR, odds ratio; CrI, credible interval.

Figure 3 Network meta-analysis results for the endpoints of adverse effects and diarrhea. The network plots show direct comparison of different therapies, with node size corresponding to sample size. The number of included studies for specific direct comparison governs the thickness of solid lines. ORs with 95% CrIs are applied to evaluate the efficacy outcomes. Note that in the upper half of the table, column treatments are compared against row treatments, whereas in the lower half of the table, row treatments are compared against column treatments. Bold data represents significant results.

Abbreviations: OR, odds ratio; CrI, credible interval.

Figure 4 Node-splitting results for ITT patient treatment success, CE patient treatment success, adverse effects, and diarrhea.

Abbreviations: ITT, intention-to-treat; CE, clinically evaluable; OR, odds ratio; CrI, credible interval.

Figure 5 Net heat plot. The size of the gray squares indicates the contribution of direct evidence (shown in the column) to the network evidence (shown in the row). The colors are associated with the change in inconsistency between direct and indirect evidence (shown in the row). Blue colors indicate an increase of inconsistency and warm colors indicate a decrease.

Abbreviations: ITT, intention-to-treat; CE, clinically evaluable.

Table 2 Surface under the cumulative ranking curve (SUCRA) results

Treatment	ITT patients – treatment success	CE patients – treatment success	Adverse effects	Diarrhea
Placebo	0.001%	21.57%	74.43%	63.17%
β-Lactams	49.67%	34.00%	86.86%	78.17%
Macrolides	83.50%	54.57%	61.86%	49.17%
Tetracyclines	–	61.14%	27.43%	53.33%
Quinolones	95.00%	83.00%	49.00%	54.17%
Sulfonamides	23.83%	3.29%	58.29%	–
Double β-lactams	54.83%	80.43%	20.57%	11.67%
Double sulfonamides	43.50%	60.57%	20.29%	40.33%

Abbreviations: ITT, intention-to-treat; CE, clinically evaluable.

Figure 6 SUCRA results.

Abbreviations: ITT, intention-to-treat; CE, clinically evaluable; SUCRA, surface under the cumulative ranking curve.

Figure 7 Clustered ranking plot of the network. The plot is based on cluster analysis of SUCRA values. Each plot shows SUCRA values for two outcomes: ITT patient treatment success, CE patient treatment success, adverse effects, and diarhoea. Each color represents a group of treatments which belongs to the same cluster. Treatments lying in the upper right corner are more effective and safer than the other treatments.

Abbreviations: ITT, intention-to-treat; CE, clinically evaluable; SUCRA, surface under the cumulative ranking curve.

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