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Meta-Analysis
. 2018 Oct 29;10(10):CD010257.
doi: 10.1002/14651858.CD010257.pub2.

Antibiotics for exacerbations of chronic obstructive pulmonary disease

Daniela J Vollenweider  1 , Anja Frei, Claudia A Steurer-Stey, Judith Garcia-Aymerich, Milo A Puhan
Affiliations
Meta-Analysis

Antibiotics for exacerbations of chronic obstructive pulmonary disease

Daniela J Vollenweider et al. Cochrane Database Syst Rev. .

Abstract

Background: Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain, as systematic reviews and clinical trials have shown conflicting results.

Objectives: To assess effects of antibiotics on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) for management of acute COPD exacerbations, as well as their effects on other patient-important outcomes (mortality, adverse events, length of hospital stay, time to next exacerbation).

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, MEDLINE, Embase, and other electronically available databases up to 26 September 2018.

Selection criteria: We sought to find randomised controlled trials (RCTs) including people with acute COPD exacerbations comparing antibiotic therapy and placebo and providing follow-up of at least seven days.

Data collection and analysis: Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients, and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised as a single group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation, and ICU patients to have a very severe exacerbation. When authors of primary studies did not report outcomes or study details, we contacted them to request missing data. We calculated pooled risk ratios (RRs) for treatment failure, Peto odds ratios (ORs) for rare events (mortality and adverse events), and mean differences (MDs) for continuous outcomes using random-effects models. We used GRADE to assess the quality of the evidence. The primary outcome was treatment failure as observed between seven days and one month after treatment initiation.

Main results: We included 19 trials with 2663 participants (11 with outpatients, seven with inpatients, and one with ICU patients).For outpatients (with mild to moderate exacerbations), evidence of low quality suggests that currently available antibiotics statistically significantly reduced the risk for treatment failure between seven days and one month after treatment initiation (RR 0.72, 95% confidence interval (CI) 0.56 to 0.94; I² = 31%; in absolute terms, reduction in treatment failures from 295 to 212 per 1000 treated participants, 95% CI 165 to 277). Studies providing older antibiotics not in use anymore yielded an RR of 0.69 (95% CI 0.53 to 0.90; I² = 31%). Evidence of low quality from one trial in outpatients suggested no effects of antibiotics on mortality (Peto OR 1.27, 95% CI 0.49 to 3.30). One trial reported no effects of antibiotics on re-exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health-related quality of life but did not show a statistically significant difference between treatment and control groups.Evidence of moderate quality does not show that currently used antibiotics statistically significantly reduced the risk of treatment failure among inpatients with severe exacerbations (i.e. for inpatients excluding ICU patients) (RR 0.65, 95% CI 0.38 to 1.12; I² = 50%), but trial results remain uncertain. In turn, the effect was statistically significant when trials included older antibiotics no longer in clinical use (RR 0.76, 95% CI 0.58 to 1.00; I² = 39%). Evidence of moderate quality from two trials including inpatients shows no beneficial effects of antibiotics on mortality (Peto OR 2.48, 95% CI 0.94 to 6.55). Length of hospital stay (in days) was similar in antibiotic and placebo groups.The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19, 95% CI 0.08 to 0.45; moderate-quality evidence; in absolute terms, reduction in treatment failures from 565 to 107 per 1000 treated participants, 95% CI 45 to 254). Results of this trial show a statistically significant effect on mortality (Peto OR 0.21, 95% CI 0.06 to 0.72; moderate-quality evidence) and on length of hospital stay (MD -9.60 days, 95% CI -12.84 to -6.36; low-quality evidence).Evidence of moderate quality gathered from trials conducted in all settings shows no statistically significant effect on overall incidence of adverse events (Peto OR 1.20, 95% CI 0.89 to 1.63; moderate-quality evidence) nor on diarrhoea (Peto OR 1.68, 95% CI 0.92 to 3.07; moderate-quality evidence).

Authors' conclusions: Researchers have found that antibiotics have some effect on inpatients and outpatients, but these effects are small, and they are inconsistent for some outcomes (treatment failure) and absent for other outcomes (mortality, length of hospital stay). Analyses show a strong beneficial effect of antibiotics among ICU patients. Few data are available on the effects of antibiotics on health-related quality of life or on other patient-reported symptoms, and data show no statistically significant increase in the risk of adverse events with antibiotics compared to placebo. These inconsistent effects call for research into clinical signs and biomarkers that can help identify patients who would benefit from antibiotics, while sparing antibiotics for patients who are unlikely to experience benefit and for whom downsides of antibiotics (side effects, costs, and multi-resistance) should be avoided.

PubMed Disclaimer

Conflict of interest statement

Claudia Steurer‐Stey has lectured for the antibiotic‐producing companies AstraZeneca, GlaxoWellcome, Merck Sharp & Dome, Pfizer, and Novartis.

JGA has received consultation and lecture fees from AstraZeneca and lecture fees from Esteve and Chiesi.

The remaining authors (DV, AF, and MAP) have no known conflicts of interest.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Antibiotics versus placebo. Outpatients, outcome: 1.2 Treatment failure within 4 weeks ‐ current drugs only.
5
5
Forest plot of comparison: 2 Antibiotics versus placebo. Inpatients, outcome: 2.2 Treatment failure within 4 weeks ‐ current drugs only.
6
6
Forest plot of comparison: 3 Antibiotics vs placebo overall, outcome: 3.1 Adverse events.
7
7
Forest plot of comparison: 2 Antibiotics versus placebo. Inpatients, outcome: 2.4 Duration of hospital stay (days).
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References

References to studies included in this review

Allegra 1991 {published data only (unpublished sought but not used)}
    1. Allegra LGC, Grossi E, Pozzi E, Blasi F, Frigerio D, Nastri A, et al. The role of antibiotics in the treatment of chronic bronchitis exacerbation: follow‐up of a multicenter study. Italian Journal of Chest Disease 1991;45(3):138‐48.
Alonso Martinez 1992 {published data only}
    1. Alonso Martinez JL, Rubio Obanos MT, Samperiz Legarre AL, Escolar Castellon F, Carrasco del Amo ME. Antibiotic treatment for acute episodes of chronic obstructive pulmonary disease [Tratamiento con antibioticos de las agudizaciones de la enfermedad pulmonar obstructiva cronica]. Anales de Medicina Interna 1992;9(8):377‐80. - PubMed
Anthonisen 1987 {published data only}
    1. Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Annals of Internal Medicine 1987;106(2):196‐204. - PubMed
Berry 1960 {published data only}
    1. Berry DG, Fry J, Hindley CP. Exacerbations of chronic bronchitis treatment with oxytetracycline. Lancet 1960;1:137‐9. [PMID: 13799872] - PubMed
Brusse‐Keizer 2009 {published and unpublished data}
    1. Brusse‐Keizer M, VanderValk P, Hendrix R, Kerstjens H, Palen J. Necessity of amoxicillin clavulanic acid in addition to prednisolone in mild‐to‐moderate COPD exacerbations. BMJ Open Respiratory Research 2014;1(1):e000052. - PMC - PubMed
    1. Brusse‐Keizer M, Valk P, Hendrix R, Kerstjens H, Palen J. Necessity of Antibiotics in Outpatients with ACOPD Exacerbation: The ABC‐Trial [PhD thesis]. Enschede: University of Twente, 2009. [ISBN 978‐90‐365‐2792‐7; doc.utwente.nl/61073/thesis_M_Brusse_Keizer.pdf]
    1. Brusse‐Keizer MG, Valk PD, Hendrix MG, Kerstjens HA, Palen J. Antibiotics in patients with a mild to moderate home‐treated COPD exacerbation: the ABC trial. American Journal of Respiratory and Critical Care Medicine 2009;179:A1493.
Daniels 2010 {published data only}
    1. Daniels JM, Schoorl M, Snijders D, Knol DL, Lutter R, Jansen HM, et al. Procalcitonin vs C‐reactive protein as predictive markers of response to antibiotic therapy in acute exacerbations of COPD. Chest 2010;138(5):1108‐15. - PubMed
    1. Daniels JM, Snijders D, Graaff CS, Vlaspolder F, Jansen HM, Boersma WG. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 2010;181(2):150‐7. - PubMed
Elmes 1957 {published data only}
    1. Elmes PC, Fletcher CM, Dutton AA. Prophylactic use of oxytetracycline for exacerbations of chronic bronchitis. British Medical Journal 1957;2:1272‐5. - PMC - PubMed
Fear 1962 {published data only}
    1. Fear EC, Edwards G. Antibiotic regimes in chronic bronchitis. British Journal of Diseases of the Chest 1962;56:153‐62. - PubMed
Hassan 2015 {published data only}
    1. Hassan, WA, Shalan I, Elsobhy M. Impact of antibiotics on acute exacerbations of COPD. Egyptian Journal of Chest Diseases and Tuberculosis 2015;64(3):579‐85.
Jørgensen 1992 {published and unpublished data}
    1. Jørgensen AF, Coolidge J, Pedersen PA, Petersen KP, Waldorff S, Widding E. Amoxicillin in treatment of acute uncomplicated exacerbations of chronic bronchitis. A double‐blind, placebo‐controlled multicentre study in general practice. Scandinavian Journal of Primary Health Care 1992;10(1):7‐11. - PubMed
Llor 2012 {published data only}
    1. Llor C, Moragas A, Hernandez S, Bayona C, Miravitlles M. Efficacy of antibiotic therapy for acute exacerbations of mild to moderate COPD. American Journal of Respiratory and Critical Care Medicine 2012;186(8):716‐23. - PubMed
Manresa 1987 {published data only}
    1. Manresa F, Blavia R, Martin R, Linares J, Rodriguez B, Verdaguer R. Antibiotics for exacerbations of chronic bronchitis. Lancet 1987;2(8555):394‐5. [PMID: 2886848] - PubMed
Nouira 2001 {published data only}
    1. Nouira S, Marghli S, Belghith M, Besbes L, Elatrous S, Abroug F. Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo‐controlled trial. Lancet 2001;358(9298):2020‐5. - PubMed
Petersen 1967 {published data only}
    1. Petersen ES, Esmann V, Honcke P, Munkner C. A controlled study of the effect of treatment on chronic bronchitis. An evaluation using pulmonary function tests. Acta Medica Scandinavica 1967;182(3):293‐305. - PubMed
Pines 1968 {published data only}
    1. Pines A, Raafat H, Plucinski K, Greenfield JS, Solari M. Antibiotic regimens in severe and acute purulent exacerbations of chronic bronchitis. British Medical Journal 1968;2(607):735‐8. - PMC - PubMed
Pines 1972 {published data only}
    1. Pines A, Raafat H, Greenfield JS, Linsell WD, Solari ME. Antibiotic regimens in moderately ill patients with purulent exacerbations of chronic bronchitis. British Journal of Diseases of the Chest 1972;66(2):107‐15. [PMID: 4556292] - PubMed
Sachs 1995 {published and unpublished data}
    1. Sachs AP, Koëter GH, Groenier KH, Waaij D, Schiphuis J, Meyboom‐de Jong B. Changes in symptoms, peak expiratory flow, and sputum flora during treatment with antibiotics of exacerbations in patients with chronic obstructive pulmonary disease in general practice. Thorax 1995;50(7):758‐63. - PMC - PubMed
van Velzen 2017 {published data only}
    1. van Velzen P, Ter Riet G, Bresser P, Baars JJ, Berg BTJ, Berg JWK, et al. Doxycycline for outpatient‐treated acute exacerbations of COPD: a randomised double‐blind placebo‐controlled trial. Lancet Respiratory Medicine 2017;5(6):492‐9. [DOI: 10.1016/S2213-2600(17)30165-0] - DOI - PubMed
Wang 2016 {published data only}
    1. Wang JX, Zhang SM, Li XH, Zhang Y, Xu ZY, Cao B. Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial. International Journal of Infectious Diseases 2016;48:40‐5. - PubMed

References to studies excluded from this review

Aitchison 1968 {published data only}
    1. Aitchison WR, Grant IW, Gould JC. Treatment of acute exacerbations in chronic bronchitis. British Journal of Clinical Practice 1968;22(8):343‐5. - PubMed
Alix 1979 {published data only}
    1. Alix M, Ardenna A, Brion G, Marquinio V, Mejia H, Oh F. Randomized, open, comparative multi‐center trial evaluating the effectiveness and toleration of doxycycline, ampicillin and cotrimoxazole in the treatment of lower respiratory infections (a collaborative study). Philippine Journal of Microbiology and Infectious Diseases 1979;8(2):123‐31.
Allan 1966 {published data only}
    1. Allan GW, Fallon RJ, Lees AW, Smith J, Tyrrell WF. A comparison between ampicillin and tetracycline in purulent chronic bronchitis. British Journal of Diseases of the Chest 1966;60(1):40‐3. - PubMed
Allegra 1996 {published data only}
    1. Allegra L, Konietzko N, Leophonte P, Hosie J, Pauwels R, Guyen JN, et al. Comparative safety and efficacy of sparfloxacin in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a double‐blind, randomised, parallel, multicentre study. Journal of Antimicrobial Chemotherapy 1996;37(Suppl A):93‐104. [PMID: 8737129] - PubMed
Alvarez‐Sala 2006 {published data only}
    1. Alvarez‐Sala JL, Kardos P, Martinez‐Beltran J, Coronel P, Aguilar L, Ceditoren AECB Working Group. Clinical and bacteriological efficacy in treatment of acute exacerbations of chronic bronchitis with cefditoren‐pivoxil versus cefuroxime‐axetil. Antimicrobial Agents and Chemotherapy 2006;50(5):1762‐7. [DOI: 10.1128/AAC.50.5.1762%E2%80%931767.2006] - DOI - PMC - PubMed
Andrijevic 2011 {published data only}
    1. Andrijevic I, Povazan D, Andrijevic L, Povazan A, Milutinov S. Treatment effects of co‐amoxiclav (Amoxiclav 2x) in acute exacerbation of severe chronic obstructive pulmonary disease: clinical evaluation [Лечење ефекти сарадње амокицлав (амокицлав 2к) у акутној погоршања тешке хроничне опструктивне болести плућа: клиничка евалуација]. Medicinski Pregled 2011;64(3‐4):178‐82. - PubMed
Anon 1969 {published data only}
    1. Anonymous. Trimethoprim‐sulphamethoxazole in chronic bronchitis. Practitioner 1969;203(218):817‐9. - PubMed
Anon 1972 {published data only}
    1. Anonymous. A further comparative trial of co‐trimoxazole in chronic bronchitis. Practitioner 1972;209(254):838‐40. - PubMed
Banerjee 2001 {published data only}
    1. Banerjee D, Hussain S, Khair O, Honeybourne D. The effects of oral clarithromycin on airway inflammation in moderate to severe chronic obstructive pulmonary disease (COPD) ‐ a double blind randomised controlled trial. European Respiratory Journal 2001;18(Suppl 33):338s.
Bekçi 2009 {published data only}
    1. Bekçi T, Kurtipek E, Kesli R, Maden E, Teke T. The effect of telithromycin on inflammatory markers in chronic obstructive pulmonary diseases. European Journal of General Medicine 2009;6(4):218‐22.
Bennion‐Pedley 1969 {published data only}
    1. Bennion‐Pedley J. Treatment of acute exacerbations of chronic bronchitis in general practice. British Journal of Clinical Practice 1969;23(7):280‐3. - PubMed
Braendli 1982 {published data only}
    1. Braendli O, Keller R, Fruehauf B. Brodimoprim(®) (RO 10‐5970) versus doxycycline in chronic bronchitis. A randomized controlled clinical trial. Chemioterapia 1982;1(4 Suppl):157.
Burgi 1975 {published data only}
    1. Burgi H. Method of evaluation of the efficiency of an antibiotic in chronic bronchitis. Application to the study of amoxicillin [Procédé d'évaluation de l'efficacité d'un antibiotique dans la bronchite chronique. Application à l'étude de l'amoxicilline]. Nouvelle Presse Medicale 1975;4(34):2453‐6. - PubMed
Burrow 1975 {published data only}
    1. Burrow G, Fox A, Daniel R. A comparative trial of Minocin (minocycline hydrochloride) and ampicillin in the treatment of acute exacerbations of chronic bronchitis. Journal of International Medical Research 1975;3:304‐8.
Chatterjee 2011 {published data only}
    1. Chatterjee S, Biswas T, Dutta A, Sengupta G, Mitra A, Kundu S. Clinical effectiveness and safety of gemifloxacin versus cefpodoxime in acute exacerbation of chronic bronchitis: a randomized, controlled trial. Indian Journal of Pharmacology 2011;43(1):40‐4. [10.4103/0253‐7613.75667] - PMC - PubMed
Chen 2000 {published data only}
    1. Chen DY, Tang XY, Chen WB. A randomized controlled study of levofloxacin and cefaclor in the treatment of lower respiratory tract infections of patients with chronic obstructive pulmonary diseases. Sichuan Medical Journal 2000;21(6):481‐3.
Christiansen 1963 {published data only}
    1. Christiansen I, Midtgaard K. A comparison of sulfonamide and penicillin treatment of acute exacerbations in chronic bronchitis [in Danish]. Ugeskrift for Laeger 1963;125(30):1041‐4. - PubMed
Citron 1969 {published data only}
    1. Citron KM, May JR. Rifamycin antibiotics in chronic purulent bronchitis. Lancet 1969;2(7628):982‐3. - PubMed
Dong 2005 {published data only}
    1. Dong L, Wang SC, Sun EH, Yu QF, Zhang Q, Wu DW. Study on efficacy of moxifloxacin in the treatment of AECB and its antimicrobial activity in vitro. Chinese Pharmaceutical Journal 2005;40(9):702‐4.
Douglas 1957 {published data only}
    1. Douglas AC, Somner AR, Marks BL, Grant IWB. Effect of antibiotics on purulent sputum in chronic bronchitis and bronchiectasis. Lancet 1957;273(6988):214‐8. [PUBMED: 13450378 ] - PubMed
Egede 1993 {published data only}
    1. Egede F, Nielsen PB, Husfeldt P. Ofloxacin and erythromycin in acute exacerbations of chronic bronchitis. Drugs 1993;45(Suppl 3):410.
Elmes 1965 {published data only}
    1. Elmes PC, King TK, Langlands JH, Mackay JA, Wallace WF, Wade OL, et al. Value of ampicillin in the hospital treatment of exacerbations of chronic bronchitis. British Medical Journal 1965;5467:904‐8. - PMC - PubMed
Fartoukh 2004 {published data only}
    1. Fartoukh M, Similowski T, Brun‐Buisson C. ANTEAB: a study of early antibiotic therapy in intensive care management of acute exacerbations of chronic obstructive lung disease. Revue des Maladies Respiratoires 2004;21(2 Pt 1):381‐9. [PMID: 15211249] - PubMed
Filipovic 2000 {published data only}
    1. Filipovic M, Pljaskic Kamenov S, Siric Z, Kamenov B, Cekic S. Erythromycin in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD). Respiratory Medicine 2000;94(Suppl A):A.10.
Francis 1960 {published data only}
    1. Francis RS, Spicer CC. Chemotherapy in chronic bronchitis. British Medical Journal 1960;1(5169):297‐303. [PUBMED: PMC1966487] - PMC - PubMed
Francis 1964 {published data only}
    1. Francis RS, May JR, Spicer CC. Influence of daily penicillin, tetracycline, erythromycin, and sulphamethoxypyridazine on exacerbations of bronchitis. A report to the Research Committee of the British Tuberculosis Association. British Medical Journal 1964;1(5385):728‐32. - PMC - PubMed
Fruensgaard 1972 {published data only}
    1. Fruensgaard K, Korner B. [Trimethoprim‐sulfamethoxazole compared with ampicillin in exacerbations of chronic bronchitis]. [Danish]. Ugeskrift for Laeger 1972;134(26):1377‐81. - PubMed
Gaillat 2007 {published data only}
    1. Gaillat J, Garau J, Sethi S, Anzueto A, Guillemot D, Weber P. Impact of telithromycin (T), azithromycin (A) and cefuroxime axetil (C) on the carriage of resistant Streptococcus pneumoniae (sp) in pts with acute exacerbation of chronic bronchitis (AECB). European Respiratory Journal 2007;30(Suppl 51):227s.
Gocke 1964 {published data only}
    1. Gocke TM, Laurenzi GA. Ampicillin therapy of acute exacerbations of chronic obstructive lung disease. Antimicrobial Agents and Chemotherapy 1964;10:686‐91. - PubMed
Goddard 2003 {published data only}
    1. Goddard RD, McNeil SA, Slayter KL, McIvor RA. Antimicrobials in acute exacerbations of chronic obstructive pulmonary disease ‐ an analysis of the time to next exacerbation before and after the implementation of standing orders. Canadian Journal of Infectious Diseases & Medical Microbiology 2003;14(5):254‐9. - PMC - PubMed
Gomez 2000 {published data only}
    1. Gomez J, Banos V, Simarro E, Lorenzo Cruz M, Ruiz Gomez J, Latour J, et al. Prospective, comparative study (1994‐1998) of the influence of short‐term prophylactic treatment with azithromycin on patients with advanced COPD [Estudio prospectivo, comparativo (1994‐1998) de la influencia de corto plazo, el tratamiento profiláctico con azitromicina en pacientes con EPOC avanzada]. Revista Española de Quimioterapia 2000;13(4):379‐83. [PMID: 11498704] - PubMed
Gotfried 2007 {published data only}
    1. Gotfried M, Busman TA, Norris S, Notario GF. Role for 5‐day, once‐daily extended‐release clarithromycin in acute bacterial exacerbation of chronic bronchitis. Current Medical Research and Opinion 2007;23(2):459‐66. [DOI: 10.1185/030079906X162827] - DOI - PubMed
Guerin 1987 {published data only}
    1. Guerin JC, Lebeau B, Leophonte P, Taytard A, Muir JF. Double blind comparative study of doxycycline versus amoxicillin in infectious exacerbations of chronic bronchitis. Medecine et Maladies Infectieuses 1987;17(12):756‐61.
Haanaes 1980 {published data only}
    1. Haanaes OC, Grimne G. Pivampicillin in exacerbations of chronic bronchitis [in Norwegian]. Tidsskrift for Den Norske Laegeforening 1980;100(32):1900‐2. - PubMed
Hansen 1986 {published data only}
    1. Hansen M. Antibiotics in the treatment of exacerbations in patients with chronic bronchitis [in Danish]. Ugeskrift for Laeger 1986;148(4):191‐3. - PubMed
Hansen 1990 {published data only}
    1. Hansen M, Evald T, Balslov S. A randomized double‐blind trial between amoxycillin and placebo in the treatment of acute exacerbations of chronic bronchitis. European Respiratory Journal 1990;3(Suppl 10):89.
Hauke 2002 {published data only}
    1. Hauke W, Kohler G, Henneicke‐Von Zepelin HH, Freudenstein J. Esberitox N as supportive therapy when providing standard antibiotic treatment in subjects with a severe bacterial infection (acute exacerbation of chronic bronchitis). A multicentric, prospective, double‐blind, placebo‐controlled study. Chemotherapy 2002;48(5):259‐66. [PMID: 12476043] - PubMed
Hopkins 1962 {published data only}
    1. Hopkins EJ, Pye AM, Solomon M, Solomon S. The treatment of exacerbations of chronic bronchitis in general practice. A comparison between oxytetracycline and oral phenoxymethyl penicillin. Journal of the College of General Practitioners 1962;5:59‐65. - PMC - PubMed
Jacobsen 2002 {published data only}
    1. Jacobsen SK, Weis N, Almdal T. Use of antibiotics in patients admitted to the hospital due to acute exacerbation of chronic obstructive pulmonary disease (COPD). European Journal of Internal Medicine 2002;13:514‐7. - PubMed
Jia 2010 {published data only}
    1. Jia B, Lu P, Huang W, Li C, Huang A, Zhou X, et al. A multicenter, randomized controlled clinical study on biapenem and imipenem/cilastatin injection in the treatment of respiratory and urinary tract infections. Chemotherapy 2010;56:285‐90. [DOI: 10.1159/000319952] - DOI - PubMed
Johnston 1961 {published data only}
    1. Johnston RN, Lockhart W, Smith DH. A trial of phenethicillin in chronic bronchitis. British Medical Journal 1961;2(5258):985‐6. [PUBMED: PMC1970174] - PMC - PubMed
Kaul 1967 {published data only}
    1. Kaul S, Verma SL, Razdan MK, Kaul SN, Razdan PN. Management of acute exacerbations in chronic bronchitis. A clinical trial. Indian Journal of Medical Sciences 1967;21(1):16‐21. - PubMed
King 1996 {published data only}
    1. King DE, Williams WC, Bishop L, Shechter A. Effectiveness of erythromycin in the treatment of acute bronchitis. Journal of Family Practice 1996;42(6):601‐5. - PubMed
Leophonte 1998 {published data only}
    1. Leophonte P, Murris‐Espin M, Berthier A, Dayan M. The place of antimicrobial chemotherapy in the treatment of adults with acute bronchitis: a double‐blind placebo‐controlled trial. Clinical Microbiology and Infection 1998;4(8):436‐41.
Lirsac 2000 {published data only}
    1. Lirsac B, Benezet O, Dansin E, Nouvet G, Stach B, Voisin C. Evaluation and symptomatic treatment of superinfectious exacerbations of COPD: preliminary study of antibiotic treatment combined with fenspiride (Pneumorel 80mg) versus placebo [L'évaluation et le traitement symptomatique des exacerbations de la MPOC surinfectious: étude préliminaire du traitement antibiotique associé à fenspiride (Pneumorel 80 mg) versus placebo]. Revue de Pneumologie Clinique 2000;56(1):17‐24. [PMID: 10740110] - PubMed
Maesen 1976 {published data only}
    1. Maesen FP, Beeuwkes H, Davies BI, Buytendijk HJ, Brombacher PJ, Wessman J. Bacampicillin in acute exacerbations of chronic bronchitis ‐ a dose‐range study. Journal of Antimicrobial Chemotherapy 1976;2(3):279‐85. - PubMed
Maesen 1980 {published data only}
    1. Maesen FP, Davies BI, Drenth BM, Elfers H. Treatment of acute exacerbations of chronic bronchitis with cefotaxime: a controlled clinical trial. Journal of Antimicrobial Chemotherapy 1980;6(Suppl A):187‐92. - PubMed
Malone 1968 {published data only}
    1. Malone DN, Gold JC, Grant IW. A comparative study of ampicillin, tetracycline hydrochloride, and methacycline hydrochloride in acute exacerbations of chronic bronchitis. Lancet 1968;2(7568):594‐6. - PubMed
May 1964 {published data only}
    1. May JR, Hurford JV, Little GM, Delves DM. Chemotherapy of chronic bronchitis with large doses of ampicillin. Lancet 1964;284(7357):444‐5. [DOI: 10.1016/S0140-6736(64)90333-2] - DOI
Miravitlles 2009 {published data only}
    1. Miravitlles M, Marin A, Monso E, Vila S, Roza C, Hervas R, et al. Efficacy of moxifloxacin in the treatment of bronchial colonisation in COPD. European Respiratory Journal 2009;34:1066‐71. [DOI: 10.1183/09031936.00195608] - DOI - PubMed
NCT00255983 {published data only}
    1. NCT00255983. Double blind trial to evaluate the efficacy and safety of faropenem medoxomil in the treatment of chronic bronchitis [Prospective, randomized, double‐blind trial to evaluate the efficacy and safety of faropenem medoxomil 600 mg po, bid for 5 days versus placebo in the treatment of acute exacerbation of chronic bronchitis]. clinicaltrials.gov/show/NCT00255983 (first received 21 November 2005).
Nicotra 1982 {published data only}
    1. Nicotra MB, Rivera M, Awe RJ. Antibiotic therapy of acute exacerbations of chronic bronchitis. A controlled study using tetracycline. Annals of Internal Medicine 1982;97(1):18‐21. - PubMed
Nonikov 2001 {published data only}
    1. Nonikov VE, Il'kovich MM, Konstantinova TD, Korovina OV, Lenkova NI, Ovcharenko SI, et al. Spiramycin and roxytromycin for the treatment of pneumonia and chronic bronchitis exacerbation [Оценка и симптоматическое лечение surinfectious обострений ХОБЛ: предварительное исследование лечения антибиотиками в сочетании с фенспирида (​​Pneumorel 80 мг) по сравнению с плацебо]. Antibiotiki i Khimioterapiia 2001;46(3):26‐8. - PubMed
Parnham 2005 {published data only}
    1. Parnham MJ, Culic O, Erakovic V, Munic V, Popovic‐Grle S, Barisic K, et al. Modulation of neutrophil and inflammation markers in chronic obstructive pulmonary disease by short‐term azithromycin treatment. European Journal of Pharmacology 2005;517:132‐43. [DOI: 10.1016/j.ejphar.2005.05.023] - DOI - PubMed
Peng 2003 {published data only}
    1. Peng CC, Aspinall SL, Good CB, Atwood CW Jr, Chang CC. Equal effectiveness of older traditional antibiotics and newer broad‐spectrum antibiotics in treating patients with acute exacerbations of chronic bronchitis. Southern Medical Journal 2003;96(10):986‐91. [PMID: 14570342] - PubMed
Pham 1964 {published data only}
    1. Pham QT, Sadoul P. Treatment of acute bronchitis patients with an attack of acute superinfection with an association of antibiotics (colistin and penicillin) [in French]. Semaine Thérapeutiqueo 1964;40(5):335‐8. - PubMed
Pines 1967 {published data only}
    1. Pines A, Raafat H. Controlled comparisons of cephaloridine with penicillin and streptomycin in chronic purulent bronchitis. Postgraduate Medical Journal 1967;43(Suppl 43):61‐3. - PubMed
Pines 1969 {published data only}
    1. Pines A, Raafat H, Plucinski K, Greenfield JS, Solari M. A comparison of erythromycin, novobiocin, tetracycline and a novobiocin‐tetracycline combination in purulent exacerbations of chronic bronchitis. British Journal of Diseases of the Chest 1969;63(4):206‐14. - PubMed
Pines 1972a {published data only}
    1. Pines A, Khaja G, Greenfield JS, Raafat H, Sreedharan KS, Linsell WD. A double‐blind comparison of slow‐release tetracycline and tetracycline hydrochloride in purulent exacerbations of chronic bronchitis. British Journal of Clinical Practice 1972;26(10):475‐6. - PubMed
Pines 1973 {published data only}
    1. Pines A. Trimethoprim‐sulfamethoxazole in the treatment and prevention of purulent exacerbations of chronic bronchitis. Journal of Infectious Diseases 1973;128:706‐9. - PubMed
Pines 1973a {published data only}
    1. Pines A, Greenfield JS, Raafat H, Sreedharan KS. A comparison of pivampicillin and ampicillin in exacerbations of chronic bronchitis. British Journal of Diseases of the Chest 1973;67(3):221‐6. - PubMed
Pines 1974 {published data only}
    1. Pines A, Raafat H, Sreedharan KS, Parker P. A comparison of pivampicillin and tetracycline in exacerbations of chronic bronchitis. Chemotherapy 1974;20(6):361‐9. - PubMed
PRITZL 1959 {published data only}
    1. Pritzl FP, Duda G. On the efficacy of butazolidine in the treatment of chronic bronchitis [Von der Wirksamkeit der butazolidine bei der Behandlung von chronischer Bronchitis]. Medizinische 1959;51:2538‐40. - PubMed
Puchelle 1975 {published data only}
    1. Puchelle E, Sobradillo V, Aug F, Sadoul P. Amoxicillin and ampicillin in the patient with chronic bronchitis. Comparative study: bacteriological, pharmacological and clinical [Amoxicilline et ampicilline chez le bronchiteux chronique. Etude comparée: bactériologique, pharmacologique et clinique]. La Nouvelle Presse Médicale 1975;4(34):2449‐52. - PubMed
Pugh 1964 {published data only}
    1. Pugh DL. Propicillin in the treatment of chronic bronchitis. British Journal of Clinical Practice 1964;18(2):81‐8. [PUBMED: 14115579] - PubMed
Rethly 1961 {published data only}
    1. Rethly E, Brenner F. Treatment of chronic purulent bronchitis with antibiotics [in German]. Zeitschrift für die Gesamte Innere Medizin und ihre Grenzgebiete 1961;16:1034‐7. - PubMed
Roede 2007 {published data only}
    1. Roede BM, Bresser P, Moussaoui R, Krouwels FH, Berg BTJ, Hooghiemstra PM, et al. Three vs. 10 days of amoxycillin–clavulanic acid for type 1 acute exacerbations of chronic obstructive pulmonary disease: a randomised, double‐blind study. Clinical Microbiology and Infection 2007;13(3):284‐90. [PUBMED: 17391383] - PubMed
Romanovskikh 2007 {published data only}
    1. Romanovskikh A, Sinopalinkov A, Ratchina S. Open label randomized, comparative trial of the efficacy of levofloxacin versus clarithromycin SR. European Respiratory Journal 2007;30(Supp 51):674s E3919.
Ross 1973 {published data only}
    1. Ross G I, Croydon EA. A winter‐long trial of ampicillin in chronic bronchitis. British Journal of Diseases of the Chest 1973;67(2):153‐60. - PubMed
Sethi 2007 {published data only}
    1. Sethi S, Kruesmann F, Haverstock D, Peroncel R, Choudri S. Correlation between eradication of infecting organism on days 3‐5 of antibiotic therapy and clinical care in patients with acute exacerbations of chronic bronchitis. European Respiratory Journal 2007;30(Suppl 51):223s.
Sethi 2010 {published data only}
    1. Sethi S, Jones PW, Schmitt Theron M, Miravitlles M, Rubinstein E, Wedzicha JA, et al. Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Respiratory Research 2010;11:10. [DOI: 10.1186/1465-9921-11-10] - DOI - PMC - PubMed
Smyllie 1972 {published data only}
    1. Smyllie HC, Lacey WB. A comparison of trimethoprim/sulphamethoxazole compound and tetracycline in exacerbations of chronic bronchitis. British Journal of Diseases of the Chest 1972;66:199‐206. - PubMed
Sohy 2002 {published data only}
    1. Sohy C, Pilette C, Niederman MS, Sibille Y. Acute exacerbation of chronic obstructive pulmonary disease and antibiotics: what studies are still needed?. European Respiratory Journal 2002;19(5):966‐75. - PubMed
Soler 2003 {published data only}
    1. Soler M, Lode H, Baldwin R, Levine JH, Schreurs AJ, Noord JA, et al. Randomised double‐blind comparison of oral gatifloxacin and co‐amoxiclav for acute exacerbations of chronic bronchitis. European Journal of Clinical Microbiology and Infectious Diseases 2003;22:144‐50. - PubMed
Soltaninejad 2016 {published data only}
    1. Soltaninejad F, Kheiri S, Habibian R, Amra A, Asgari‐Savadjani S. Evaluation effects of nebulized gentamicin in exacerbation of chronic obstructive lung disease. Journal of Research in Medical Sciences 2016;21:56. [DOI: 10.4103/1735-1995.187278] - DOI - PMC - PubMed
Stolz 2007 {published data only}
    1. Stolz D, Christ‐Crain M, Bingisser R, Leuppi J, Miedinger D, Muller C, et al. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin‐guidance with standard therapy. Chest 2007;131(1):9‐19. [DOI: 10.1378/chest.06-1500] - DOI - PubMed
Suzuki 2001 {published data only}
    1. Suzuki T, Yanai M, Yamaya M, Satoh‐Nakagawa T, Sekizawa K, Ishida S, et al. Erythromycin and common cold in COPD. Chest 2001;120(3):730‐3. [PMID: 11555501] - PubMed
Tremolieres 2000 {published data only}
    1. Tremolieres F. Augmentin 1 g/125 mg 2 times a day in acute exacerbations of chronic bronchitis [in French]. Presse Medicale 2000;29(26 Suppl):11‐3. - PubMed
Williams 1981 {published data only}
    1. Williams HN, John DW, Brown P, Rose AJ. A double blind comparison of talampicillin and ampicillin in the treatment of exacerbations of chronic bronchitis in general practice. British Journal of Clinical Practice 1981;35(4):147‐52. - PubMed
Wilson 2004 {published data only}
    1. Wilson R, Allegra L, Huchon G, Izquierdo J‐L, Jones P, Schaberg T, et al. Short‐term and long‐term outcomes of moxifloxacin compared to standard antibiotic treatment in acute‐exacerbations of chronic bronchitis. Chest 2004;125(3):953‐64. - PubMed
Wilson 2011 {published data only}
    1. Wilson R, Anzueto A, Miravitlles M, Arvis P, Haverstock D, Trajanovic M, et al. Moxifloxacin (MXF) vs. amoxicillin/clavulanic acid (AMC) in acute exacerbations of COPD (AECOPD): results of a large clinical trial with a novel endpoint. Respirology 2011;16(Suppl 2):195.
Wilson 2012 {published data only}
    1. Wilson R, Anzueto A, Miravitlles M, Arvis P, Alder J, Haverstock D, et al. Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results. European Respiratory Journal 2012;40:17‐27. - PMC - PubMed
Zapulla 1988 {published data only}
    1. Zappulla G, Baratelli E, Bettini R, Mamolo G, Quadrelli C, Piccinelli M. Clinical evaluation of the efficacy and tolerability of 2 acyl‐ureido‐penicillins (mezlocillin and piperacillin) in the treatment of chronic bronchitis during acute phase [Valutazione clinica dell'efficacia e della tollerabilitą di due acil‐ureido‐penicilline (Mezlocillina e Piperacillina) nel trattamento delle bronchiti croniche riacutizzate]. Archivio Monaldi Per Le Malattie Del Torace 1988;43(3):279‐88. - PubMed
Zervos 2005 {published data only}
    1. Zervos M, Breen JD, Jogensen D, Goodrich JM. Azithromycin microspheres (AZ‐M) are as effective as levofloxacin (LEV) in subjects with moderate to very severe COPD. Infectious Diseases in Clinical Practice 2005;13:115‐21.

References to ongoing studies

NCT01091493 {published data only}
    1. NCT01091493. Antibiotic or not in non‐purulent exacerbations of COPD: a trial of security and efficacy (AEPOC‐ATB). https://clinicaltrials.gov/ct2/show/NCT01091493 (first posted 24 March 2010).
NCT01892488 {published data only}
    1. NCT01892488. Study to demonstrate that antibiotics are not needed in moderate acute exacerbations of COPD. https://clinicaltrials.gov/ct2/show/NCT01892488 (first posted 4 July 2013). - PMC - PubMed
NCT03262142 {published data only}
    1. NCT03262142. Targeted antibiotics for chronic obstructive pulmonary disease (Target‐ABC). clinicaltrials.gov/ct2/show/NCT03262142 (first received 25 August 2017).

Additional references

Bafadhel 2011
    1. Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, et al. Acute exacerbations of COPD: identification of biological clusters and their biomarkers. American Journal of Respiratory Critical Care Medicine 2011;184(6):662‐71. - PubMed
Daniels 2010b
    1. Daniels JM, Schoorl M, Snijders D, Knol DL, Lutter R, Jansen HM, et al. Procalcitonin vs C‐reactive protein as predictive markers of response to antibiotic therapy in acute exacerbations of COPD. Chest 2010;138(5):1108‐15. - PubMed
Donath 2013
    1. Donath E, Chaudhry A, Hernandez‐Aya LF, Lit L. A meta‐analysis on the prophylactic use of macrolide antibiotics for the prevention of disease exacerbations in patients with chronic obstructive pulmonary disease. Respiratory Medicine 2013;107:1385‐92. - PubMed
Garcia‐Aymerich 2011
    1. Garcia‐Aymerich J, Gómez FP, Benet M, Farrero E, Basagaña X, Gayete À, et al. Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes. Thorax 2011;66(5):430‐7. - PubMed
GOLD 2018
    1. Global Initiative for Asthma. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2018 report). goldcopd.org/wp‐content/uploads/2017/11/GOLD‐2018‐v6.0‐FINAL‐revised‐20‐... (accessed prior to 22 October 2018).
GRADEpro GDT [Computer program]
    1. Developed by Evidence Prime, Inc. Available from gradepro.org. GRADEpro Guideline Development Tool. Developed by Evidence Prime, Inc. Available from gradepro.org, McMaster University, 2015.
Guyatt 2011
    1. Guyatt G, Oxman AD, Akl E, Kunz R, Vist G, Brozek J, et al. GRADE guidelines 1. Introduction ‐ GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64(4):383‐94. - PubMed
Herath 2013
    1. Herath SC, Poole P. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD). Cochrane Database of Systematic Reviews 2013, Issue 11. [DOI: 10.1002/14651858.CD009764.pub2; CD009764] - DOI - PubMed
Higgins 2011
    1. 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 www.cochrane‐handbook.org.
Jones 2008
    1. Jones RC, Dickson‐Spillmann M, Mather MJ, Marks D, Shackell BS. Accuracy of diagnostic registers and management of chronic obstructive pulmonary disease: the Devon primary care audit. Respiratory Research 2008;18(9):62. - PMC - PubMed
Labaki 2017
    1. Wassim WL, MeiLan KH. Antibiotics for COPD exacerbations. Lancet 2017;5:461‐2. - PMC - PubMed
Lin 2018
    1. Lin C, Pang Q. Meta‐analysis and systematic review of procalcitonin‐guided treatment in acute exacerbation of chronic obstructive pulmonary disease. Clinical Respiratory Journal 2018;12(1):10‐5. - PubMed
Mathioudakis 2017
    1. Mathioudakis AG, Chatzimavridou‐Grigoriadou V, Corlateanu A, Vestbo J. Clinical effectiveness of procalcitonin‐based protocols to initiate or discontinue antibiotics in COPD exacerbations: a systematic review and meta‐analysis. European Respiratory Review 2017;26(143). - PMC - PubMed
NICE 2010
    1. National Institute for Health and Clinical Excellence (NICE). Chronic obstructive pulmonary disease in over 16s: diagnosis and management. Clinical guideline [CG101]. www.nice.org.uk/guidance/cg101 (accessed prior to 26 April 2018).
NICE 2018
    1. NICE. Pathway for COPD exacerbations. pathways.nice.org.uk/pathways/chronic‐obstructive‐pulmonary‐disease/mana... (accessed 30 June 2018).
Patel 2002
    1. Patel IS, Seemungal TA, Wilks M, Lloyd‐Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 2002;57(9):759‐64. - PMC - PubMed
Pretto 2012
    1. Pretto JJ, McDonald VM, Wark PA, Hensley MJ. A multicentre audit of inpatient management of acute exacerbations of COPD: comparison with clinical guidelines. Internal Medicine Journal 2012;42(4):380‐7. - PubMed
Puhan 2007
    1. Puhan MA, Vollenweider D, Latshang T, Steurer J, Steurer‐Stey C. Exacerbations of chronic obstructive pulmonary disease: when are antibiotics indicated? A systematic review. Respiratory Research 2007;4(8):30. - PMC - PubMed
Puhan 2008
    1. Puhan MA, Vollenweider D, Steurer J, Bossuyt PM, Ter Riet G. Where is the supporting evidence for treating mild to moderate chronic obstructive pulmonary disease exacerbations with antibiotics? A systematic review. BMC Medicine 2008;6:28. - PMC - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rodriguez‐Roisin 2000
    1. Rodriguez‐Roisin R. Toward a consensus definition for COPD exacerbations. Chest 2000;117(5 Suppl 2):398S‐401S. - PubMed
Saint 1995
    1. Saint S, Bent S, Vittinghoff E, Grady D. Antibiotics in chronic obstructive pulmonary disease exacerbations. A meta‐analysis. JAMA 1995;273(12):957‐60. - PubMed
Schuetz 2012
    1. Schuetz P, Müller B, Christ‐Crain M, Stolz D, Tamm M, Bouadma L, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database of Systematic Reviews 2012, Issue 9. [DOI: 10.1002/14651858.CD007498] - DOI - PMC - PubMed
Seemungal 2001
    1. Seemungal T, Harper‐Owen R, Bhowmik A, Moric I, Sanderson G, Message S, et al. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. American Journal of Respiratory Critical Care Medicine 2001;164(9):1618‐23. - PubMed
Seibold 2016
    1. Heidi S, Achim Z, Torsten H. Model‐based recursive partitioning for subgroup analyses. International Journal of Biostatistics 2016;12(1):45–63. - PubMed
Sethi 2004
    1. Sethi S. Bacteria in exacerbations of chronic obstructive pulmonary disease: phenomenon or epiphenomenon?. Proceedings of the American Thoracic Society 2004;1(2):109‐14. - PubMed
WHO Factsheet no. 194
    1. World Health Organization. Antimicrobial resistance. www.who.int/en/news‐room/fact‐sheets/detail/antimicrobial‐resistance (accessed prior to 27 April 2018).
Zhang 2017
    1. Zhang HL, Tan M, Qiu AM, Tao Z, Wang CH. Antibiotics for treatment of acute exacerbation of chronic obstructive pulmonary disease: a network meta‐analysis. BMC Pulmonary Medicine 2017;17(1):196. - PMC - PubMed

References to other published versions of this review

Ram 2006
    1. Ram FS, Rodriguez‐Roisin R, Granados‐Navarrete A, Garcia‐Aymerich J, Barnes NC. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 2. [DOI: 10.1002/14651858.CD004403.pub2] - DOI - PubMed
Vollenweider 2012
    1. Vollenweider DJ, Jarrett H, Steurer‐Stey CA, Garcia‐Aymerich J, Puhan MA. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2012, Issue 12. [DOI: 10.1002/14651858.CD010257] - DOI - PubMed

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