Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. PREDICTIVE VALUE OF GLASGOW COMA SCORE FOR AWAKENING AFTER OUT-OF-HOSPITAL CARDIAC ARREST Clinical and Bacteriological Efficacy in Treatment of Acute Exacerbations of Chronic Bronchitis with Cefditoren-Pivoxil versus Cefuroxime-Axetil Factors affecting survival of hospitalised patients with COPD A comparison between ampicillin and tetracycline in purulent chronic bronchitis. Three vs. 10 days of amoxycillin-clavulanic acid for type 1 acute exacerbations of chronic obstructive pulmonary disease: a randomised, double-blind study. Role for 5‑day, once-daily extended-release clarithromycin in acute bacterial exacerbation of chronic bronchitis Severe community-acquired pneumonia: assessment of microbial aetiology as mortality factor Erythromycin and common cold in COPD. Short-term and long-term outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Viral Antibody Levels and Clinical Status in Acute Exacerbations of Chronic Bronchitis: a Controlled Prospective Study* 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. Amoxicillin in treatment of acute uncomplicated exacerbations of chronic bronchitis. A double-blind, placebo-controlled multicentre study in general practice. Comparative safety and efficacy of sparfloxacin in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a double-blind, randomised, parallel, multicentre study. Esberitox® N as Supportive Therapy when Providing Standard Antibiotic Treatment in Subjects with a Severe Bacterial Infection (Acute Exacerbation of Chronic Bronchitis) Rifamycin antibiotics in chronic purulent bronchitis. A winter-long trial of ampicillin in chronic bronchitis. Randomised Double-Blind Comparison of Oral Gatifloxacin and Co-amoxiclav for Acute Exacerbation of Chronic Bronchitis Antibiotic therapy of acute exacerbations of chronic bronchitis. A controlled study using tetracycline. Antibiotic regimens in severe and acute purulent exacerbations of chronic bronchitis. Trimethoprim-sulfamethoxazole in the treatment and prevention of purulent exacerbations of chronic bronchitis. Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo-controlled trial Value of ampicillin in the hospital treatment of exacerbations of chronic bronchitis. Modulation of neutrophil and inflammation markers in chronic obstructive pulmonary disease by short-term azithromycin treatment. A comparison of pivampicillin and ampicillin in exacerbations of chronic bronchitis. [Prospective, comparative study (1994-1998) of the influence of short-term prophylactic treatment with azithromycin on patients with advanced COPD]. Effectiveness of erythromycin in the treatment of acute bronchitis. [Evaluation and symptomatic treatment of surinfectious exacerbations of COPD: preliminary study of antibiotic treatment combined with fenspiride (Pneumorel 80mg) versus placebo]. A comparison of erythromycin, novobiocin, tetracycline and a novobiocin-tetracycline combination in purulent exacerbations of chronic bronchitis. Course and prognosis of chronic obstructive lung disease. A prospective study of 200 patients. A comparative study of ampicillin, tetracycline hydrochloride, and methacycline hydrochloride in acute exacerbations of chronic bronchitis. Antibiotic regimens in moderately ill patients with purulent exacerbations of chronic bronchitis. Evidence Base for Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease A comparison of pivampicillin and tetracycline in exacerbations of chronic bronchitis.
BACKGROUND Therapy with antibiotics influences recovery only in selected cases of COPD exacerbations . We evaluated the efficacy and safety of procalcitonin guidance compared to st and ard therapy with antibiotic prescriptions in patients experiencing exacerbations of COPD . METHODS A total of 208 consecutive patients requiring hospitalization for COPD exacerbation were r and omized at the index exacerbation to procalcitonin-guided or st and ard antibiotic therapy . Patients receiving procalcitonin-guided therapy were treated with antibiotics according to serum procalcitonin levels ; st and ard-therapy patients received antibiotics according to the attending physician . The primary outcome was the antibiotic exposure at the index exacerbation and the subsequent antibiotic requirement for COPD exacerbation within 6 months . Secondary outcomes were clinical recovery , symptom scores , length of hospitalization , ICU stay , death , lung function , exacerbation rate , and time to next exacerbation . RESULTS At the index exacerbation , procalcitonin guidance reduced antibiotic prescription ( 40 % vs 72 % , respectively ; p < 0.0001 ) and antibiotic exposure ( relative risk [ RR ] , 0.56 ; 95 % confidence interval [ CI ] , 0.43 to 0.73 ; p < 0.0001 ) compared to st and ard therapy . Moreover , procalcitonin guidance at the index exacerbation allowed a significant sustained reduction in total antibiotic exposure for up to 6 months ( RR , 0.76 ; 95 % CI , 0.64 to 0.92 ; p = 0.004 ) . Clinical outcome and improvement in FEV(1 ) at 14 days and 6 months did not differ between groups . Within 6 months , the exacerbation rate ( 0.62 vs 0.64 , respectively ) , the rehospitalization rate ( 0.21 vs 0.24 , respectively ) , and mean ( + /- SD ) time to the next exacerbation ( 70.0 + /- 46.1 vs 70.4 + /- 51.9 days , respectively ; p = 0.523 ) were similar in both groups . CONCLUSIONS Procalcitonin guidance for exacerbations of COPD offers a sustained advantage over st and ard therapy in reducing antibiotic use for up to 6 months with a number-needed-to-treat of 3 The Glasgow coma score ( GCS ) during days 1 - 6 after cardiac arrest was used to predict neurological outcome in 360 resuscitated victims of out-of-hospital cardiac arrest . A predictive rule based on the best GCS of 216 patients resuscitated in 1983 - 84 ( prediction group ) was constructed , and its predictive power was tested on 133 patients treated in 1985 ( test group ) .  Neurological outcome was correctly predicted 2 days after cardiac arrest in 80 % of the prediction group , with a best GCS of 10 or above and 4 or below as cutoff points . For patients with a best GCS of 5 - 9 , prediction of outcome was possible 6 days after cardiac arrest , with a best GCS of 8 during the first 6 days as the single cutoff point . The rule was then vali date d in the test group : the sensitivity was 96 % ; the specificity 86 % ; the negative predictive value 97 % ; and the positive predictive value 77 % . These data suggest that this simple GCS-based rule can be helpful in predicting outcome in patients resuscitated after out-of-hospital cardiac arrest , but confirmation of these data is required in a prospect i ve study in a larger number of patients ABSTRACT A r and omized , double-blind , double-dummy trial was performed comparing 200 mg of cefditoren-pivoxil twice daily for 5 days versus st and ard cefuroxime-axetil treatment ( 250 mg twice daily for 10 days ) of Anthonisen type I or II acute exacerbations of chronic bronchitis . The modified intention-to-treat population included 541 patients . Patients were assessed during therapy , at the end of therapy ( visit 3 ; primary evaluation time point ) , and at follow-up . Clinical success was obtained in 79.9 % of the 264 patients included in the cefditoren-pivoxil group and in 82.7 % of the 277 patients in the cefuroxime-axetil group ( treatment difference , 95 % confidence interval [ CI ] : −2.8 , −9.7 to 3.6 % ) . Treatment clinical effects were more clearly seen in sputum signs ( decreasing volume and purulence from approximately 80 % to approximately 10 % of the patients ) . At the end of treatment , exploratory analysis of the per-pathogen bacteriological response showed 72.8 % ( of 103 isolates ) in the cefditoren-pivoxil arm versus 67.0 % ( of 94 isolates ) in the cefuroxime-axetil group ( treatment difference ; 95 % CI : 5.8 , −7.0 to 18.6 % ) . Globally , the per-pathogen bacteriological response correlated well with clinical success : 83.5 % of 164 baseline isolates from patients with a clinical success were eradicated or presumably eradicated , in contrast to only 3 % of 33 isolates from patients with a clinical failure . Clinical success in patients infected with Haemophilus influenzae , the most frequent isolate , was 84 % ( of 50 ) and 82.5 % ( of 40 ) ( treatment difference ; 95 % CI : 1.5 , −14 to 17 % ) in the cefditoren-pivoxil versus the cefuroxime-axetil group . Although this study does not prove that either drug is better than a placebo , cefditoren-pivoxil and the st and ard 10-day cefuroxime-axetil course had similar point estimates of success in acute exacerbations of chronic bronchitis Factors determining in-hospital mortality and long-term survival of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) are not precisely understood . The aim of the present study was to assess the parameters related to in-hospital mortality and long-term survival after hospitalisation of patients with AE COPD . Clinical and epidemiological parameters on admission in 205 consecutive patients hospitalised with AE COPD were prospect ively assessed . Patients were followed-up for 3 yrs . Factors determining short- and long-term mortality were analysed . In total , 17 patients ( 8.3 % ) died in hospital . In-hospital mortality was significantly associated with lower arterial oxygen tension ( Pa , O2 ) , higher carbon dioxide arterial tension , lower arterial oxygen saturation and longer hospital stay . The overall 6-month mortality rate was 24 % , with 1- , 2- and 3-yr mortality rates of 33 % , 39 % and 49 % , respectively . Cox regression analysis revealed that long-term mortality was associated with longer disease duration ( relative risk ( RR ) = 1.158 ) , lower albumin ( RR = 0.411 ) , lower Pa , O2 ( RR = 0.871 ) and lower body mass index ( RR = 0.830 ) . When the model was run for the time elapsed since first hospitalisation , it also appeared as statistically significant ( RR = 1.195 ) . These findings show that patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease have poor short- and long-term survival . Prediction of survival status may be enhanced by considering arterial oxygen tension , albumin , body mass index , disease duration and time elapsed since the first hospitalisation Summary In a double-blind trial of  ampicillin and tetracycline  in chronic bronchitics with purulent sputum , 44 patients received ampicillin 1 g.  per day for five days and 43 patients received tetracycline 1 g.  per day for five days . Purulence of sputum was lessened in 37 ( 84 per cent . ) of the 44 ampicillin patients and in 35 ( 81 per cent . ) of the 43  tetracycline  patients ; but whereas the purulence was completely eliminated in only 19 ( 43 per cent . ) of the tetracycline patients , it was eliminated completely in 28 ( 64 per cent . ) of the ampicillin patients . H. influenz˦ , Strep . pneumoni˦ and other potential pathogens disappeared from the sputum of patients in both series with approximately equal frequency The optimal duration of antibiotic treatment for acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) is unknown . This study compared the outcome of treatment for 3 vs. 10 days with amoxycillin-clavulanic acid of hospitalised patients with AE COPD who had improved substantially after initial therapy for 3 days . Between November 2000 and December 2003 , 56 patients with AE COPD were enrolled in the study . Unfortunately , because of the low inclusion rate , the trial was discontinued prematurely . Patients were treated with oral or intravenous amoxycillin-clavulanic acid . Patients who showed improvement after 72 h were r and omised to receive oral amoxycillin-clavulanic acid 625 mg or placebo , four times daily for 7 days . The primary outcome measure of the study was clinical cure after 3 weeks and 3 months . Of 46 patients included in the final analysis , 21 were in the 3-day treatment group and 25 were in the 10-day treatment group . After 3 weeks , 16 ( 76 % ) of 21 patients in the 3-day treatment group were cured , compared with 20 ( 80 % ) of 25 in the 10-day treatment group ( difference -3.8 % ; 95 % CI -28 to 20 ) . After 3 months , 13 ( 62 % ) of 21 patients were cured , compared with 14 ( 56 % ) of 25 ( difference 5.9 % ; 95 % CI -23 to 34 ) . Microbiological success , symptom recovery , the use of corticosteroids , the duration of oxygen therapy and the length of hospital stay were comparable for both treatment groups . It was concluded that 3-day treatment with amoxycillin-clavulanic acid can be a safe and effective alternative to the st and ard 10-day treatment for hospitalised patients with AE COPD who have improved after initial therapy for 3 days ABSTRACT Background : Clarithromycin is commonly dosed for 7 or more days in patients with acute bacterial exacerbation of chronic bronchitis ( ABECB ) . Studies with other antibiotics have shown equivalent efficacy , reduced/similar frequency of adverse events , improved adherence and patient satisfaction , and lower treatment costs with a shorter treatment course . Patients and methods : The study population was derived from two multicenter , r and omized , double-blind ( North America)/single-blind ( France ) comparative trials in which out patients at least 35 years old with a presumptive diagnosis of obstructive ABECB were r and omized to receive clarithromycin extended-release ( ER ) 1000 mg once daily for 5 days or a comparator agent – clarithromycin immediate-release ( IR ) 500 mg twice daily for 7 days ( in North America ) or telithromycin 800 mg once daily for 5 days ( in France ) . Results : A total of 818 patients were r and omized ( 411 to  clarithromycin  ER and 407 to a comparator agent ) . The clinical cure rate in clinical ly evaluable patients at the follow-up visit was 90 % each for the clarithromycin ER group ( 318/353 ) and the comparator group ( 318/355 ) . The patient bacteriological cure rate and the overall target pathogen eradication rate in clinical ly and bacteriologically evaluable patients were each 92 % for the clarithromycin ER group ( 155/168 and 189/205 , respectively ) and 93 % for the comparator group ( 147/158 and 183/197 , respectively ) at the follow-up visit . The study drugs were generally well tolerated , with < 2 % of patients discontinuing their treatment prematurely due to a drug-related adverse event . The incidence of drug-related adverse events was 18 % ( 73/411 ) in the clarithromycin ER group and 24 % ( 97/407 ) in the comparator group . Clarithromycin ER-treated patients reported statistically significantly fewer episodes of abdominal pain than did patients treated with a comparator agent ( 0.2 % vs. 1.7 % , respectively ; p = 0.037 ) . This combined analysis is limited by differing blinding methods , comparator agents , and their duration of administration . Furthermore , many patients were excluded from the clinical ly and bacteriologically evaluable group due to lack of a pretreatment target pathogen . Conclusion : A once daily , 5‑day clarithromycin ER regimen appears to be a suitable choice for treating patients with ABECB Community-acquired pneumonia ( CAP ) remains a major cause of mortality . The aetiology of CAP has rarely been identified as a mortality risk factor . A prospect i ve study was conducted to assess the prognostic factors of CAP patients admitted to the intensive care unit ( Centre Hospitalier Departmental Félix Guyon , St Denis de la Réunion , France ) , with a special emphasis on microbial aetiology . All variables assessing severity were collected , with a special emphasis on microbial investigations . Among 112 immunocompetent patients ( mean±sd age 54.7±15.1 yrs ) , 84 % were male . Severity of CAP was demonstrated by mortality rate ( 43 % ) , shock ( 48 % ) , simplified acute physiology score ( SAPS ; 46.4±21.6 ) and mechanical ventilation support ( 82 % ) . Mean risk factor score was 2.2±1.2 . Microbiological identification was obtained in 78.6 % of cases , with positive blood culture in 33 % . Most frequently , microbial agents were Streptococcus pneumoniae and Klebsiella pneumoniae ( 42 % and 22 % , respectively ) . The univariate analysis recorded the usual mortality variables : age , alcohol consumption , SAPS , shock , mechanical ventilation , positive end expiratory pressure level , positive blood culture , multilobar infiltrates on chest radiograph , neutropenia , and acidosis , and found K. pneumoniae ( versus S. pneumoniae , and all CAP ) as a mortality factor . The multivariate analysis demonstrated that septic shock ( relative risk ( RR ) 141 ) , K. pneumoniae CAP ( RR 27 ) , SAPS ( RR 10.7 ) and positive blood culture ( RR 2.7 ) were independent factors related to death . In conclusion , the present study found that the microbial aetiology , Klebsiella pneumoniae , was an independent risk factor for mortality in severe community-acquired pneumonia STUDY OBJECTIVES To investigate whether erythromycin therapy lowers the frequency of the common cold and subsequent exacerbation in patients with COPD . DESIGN Prospect i ve , r and omized , controlled , but not blinded , trial . PATIENTS One hundred nine patients with COPD were enrolled into the study . Patients were r and omly assigned to erythromycin therapy or to no active treatment in September 1997 . Patients then were observed for 12 months , starting in October , during which time the risk and frequency of catching common colds and COPD exacerbations were investigated . Fifty-five patients received erythromycin at study entry ( erythromycin group ) . The remaining 54 patients received no active treatment ( control group ) . MEASUREMENTS AND RESULTS The mean ( + /- SE ) number of common colds for 12 months was significantly lower in the erythromycin group than in the control group ( 1.24 + /- 0.07 vs 4.54 + /- 0.02 , respectively , per person ; p = 0.0002 ) . Forty-one patients ( 76 % ) in the control group experienced common colds more than once , compared to 7 patients ( 13 % ) in the erythromycin group . The relative risk of developing two or more common colds in the control group compared with that in the erythromycin group was 9.26 ( 95 % confidence interval [ CI ] , 3.92 to 31.74 ; p = 0.0001 ) . Thirty patients ( 56 % ) in the control group and 6 patients ( 11 % ) in the erythromycin group had one or more exacerbations . The relative risk of experiencing an exacerbation in the control group compared with that in the erythromycin group was 4.71 ( 95 % CI , 1.53 to 14.5 ; p = 0.007 ) . Significantly more patients were hospitalized due to exacerbations in the control group than in the erythromycin group ( p = 0.0007 ) . CONCLUSION Erythromycin therapy has beneficial effects on the prevention of exacerbations in COPD patients STUDY OBJECTIVES To compare the effectiveness of oral moxifloxacin with st and ard antibiotic therapy in acute exacerbation of chronic bronchitis ( AECB ) . DESIGN Multicenter , multinational , r and omized , double-blind study of two parallel treatment arms . PATIENTS Out patients > or= 45 years old with stable chronic bronchitis , smoking history of > or= 20 pack-years , two or more AECBs in the previous year , and FEV(1 ) < 85 % of predicted value . Patients were enrolled when in a stable condition , and patients with exacerbations within 12 months of enrollment were r and omized . INTERVENTIONS R and omization ( stratified on steroid use ) between moxifloxacin ( 400 mg qd for 5 days ) and st and ard therapy ( amoxicillin [ 500 mg tid for 7 days ] , clarithromycin [ 500 mg bid for 7 days ] , or cefuroxime-axetil [ 250 mg bid for 7 days ] ) . MEASUREMENTS Assessment at enrollment , r and omization ( Anthonisen type 1 exacerbation ) , 7 to 10 days after treatment , and monthly until next AECB or up to 9 months . The primary efficacy variable was clinical success ( sufficient improvement , no alternative antimicrobial therapy required ) 7 to 10 days after therapy . Secondary predefined end points were clinical cure ( return to pre-exacerbation status ) , further antimicrobial use , time to next AECB , and bacteriologic success . RESULTS Three hundred fifty-four patients received moxifloxacin , and 376 patients received st and ard therapy . At 7 to 10 days after therapy , clinical success rates were similar in intention-to-treat ( ITT ) patients ( 95 % confidence interval [ CI ] , - 0.7 to 9.5 ) and per- protocol ( PP ) patients ( 95 % CI , - 3.0 to 8.5 ) . Moxifloxacin showed superior clinical cure rates over st and ard therapy in both ITT patients ( 95 % CI , 1.4 to 14.9 ) and PP patients ( 95 % CI , 0.3 to 15.6 ) , and higher bacteriologic success in microbiologically valid patients ( 95 % CI , 0.4 to 22.1 ) . Fewer ITT patients required antimicrobials after treatment with moxifloxacin than st and ard therapy ( p < 0.01 ) . Time to next exacerbation was longer with moxifloxacin ; median and mean times to new AECBs in ITT patients who did not require any further antibiotics were 131.0 days and 132.8 days in moxifloxacin , and 103.5 days and 118.0 days in st and ard therapy , respectively ( p = 0.03 ) . The occurrence of failure , new exacerbation , or any further antibiotic was less frequent in moxifloxacin-treated patients for up to 5 months of follow-up ( p = 0.03 ) . CONCLUSIONS Moxifloxacin was equivalent to st and ard therapy for clinical success and showed superiority over st and ard therapy in clinical cure , bacteriologic eradication , and long-term outcomes The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a r and omized , double-blinded , crossover trial . Exacerbations were defined in terms of increased dyspnea , sputum production , and sputum purulence . Exacerbations were followed at 3-day intervals by home visits , and those that resolved in 21 days were design ated treatment successes . Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary , and those in which the patient 's condition deteriorated so that intervention was necessary . Over 3.5 years in 173 patients , 362 exacerbations were treated , 180 with placebo and 182 with antibiotic .  The success rate with placebo was 55 % and with antibiotic 68 % . The rate of failure with deterioration was 19 % with placebo and 10 % with antibiotic . There was a significant benefit associated with antibiotic .  Peak flow recovered more rapidly with antibiotic treatment than with placebo .  Side effects were uncommon and did not differ between antibiotic and placebo We carried out a comprehensive microbiological study of the upper and lower airways in patients with severe exacerbations of chronic obstructive pulmonary disease ( COPD ) requiring mechanical ventilation in order to describe microbial patterns and analyze their clinical significance .  Quantitative cultures of tracheobronchial aspirates ( TBAs ) , bronchoscopically retrieved protected specimen brush ( PSB ) and bronchoalveolar lavage fluid ( BALF ) at admission to the ICU and after 72 h , as well as serology for bacteria and respiratory viruses were performed . Fifty patients ( mean age 68 + /- 8 , 46 males ) were studied prospect ively . Potentially pathogenic microorganisms ( PPMs ) and /or a positive serology were present in 36 of 50 ( 72 % ) patients , including 12 ( 33 % ) polymicrobial cases . Only six ( 12 % ) had no pathogen in any sample in the absence of antimicrobial pretreatment . Microbial patterns corresponded to community-acquired pathogens ( Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis ) in 19 of 34 ( 56 % ) and to gram-negative enteric bacilli ( GNEB ) , Pseudomonas , and Stenotrophomonas spp . in 15 of 34 ( 44 % ) of isolates . Chlamydia pneumoniae and respiratory viruses were found in 18 % and 16 % of investigations , respectively . Repeated investigation after 72 h in 19 patients with PPMs in the initial investigation revealed eradication of virtually all isolates of community-acquired pathogens and GNEB but persistence of three of five Pseudomonas spp . and both Stenotrophomonas spp . as well as the emergence of new GNEB , Pseudomonas and Stenotrophomonas spp . Clinical parameters neither predicted the presence of PPMs nor of GNEB and Pseudomonas/Stenotrophomonas spp . Nevertheless , severe pneumonia attributable to initially isolated pathogens occurred in two patients with severe COPD exacerbation . We conclude that pathogens were more frequently present than previously reported . The rate of GNEB and Pseudomonas/Stenotrophomonas spp . isolates was high . The presence of pathogens was clinical ly unpredictable . Thus , in this population of patients with severe exacerbations of COPD , it may be advisable to obtain respiratory sample s and to treat according to diagnostic results . Further studies are warranted to clarify this issue A controlled prospect i ve study was made of a group of patients with chronic bronchitis , in which serum antibodies against a group of viruses and Mycoplasma pneumoniae were estimated at regular intervals . Sixteen significant rises in antibody titre were shown , of which eight were associated with clinical acute exacerbations of bronchitis . In individual patients no correlation was found between the number of acute exacerbations or the aetiological agent and persistent change in ventilatory function as expressed by the F.E.V.0.75 . This study was compared with the results of a previous parallel investigation of the same patients done to study the significance of rhinovirus infections . In the present investigation 12 % of the acute exacerbations were associated with the 11 agents tested compared with 14 % associated with rhinoviruses in the earlier work BACKGROUND --Bacterial infections of the lower airways during an exacerbation in patients with asthma or chronic obstructive pulmonary disease ( COPD ) may be the cause of an exacerbation or the consequence of a viral infection or an increase in airways limitation . To determine whether bacterial infection is an important component in the pathogenesis of an exacerbation , the effects of antimicrobial treatment must be studied . METHODS -- Patients with asthma or COPD seen in general practice were studied in a double blind r and omised manner to investigate whether the antimicrobial drugs amoxicillin ( 500 mg three times daily ) , cotrimoxazole ( 960 mg twice daily ) , or a placebo , each when added to a short course of oral corticosteroids , can accelerate recovery from exacerbations . Patients were instructed to contact their own physician early in the morning when complaints of increased shortness of breath , wheezing , or exacerbations of cough with or without sputum production occurred . Treatment effects were evaluated over the next 14 days by study ing symptom scores ( wheeze , dyspnoea , cough with and without mucus production , and awakening with dyspnoea ) , peak expiratory flow values ( PEF , expressed as % predicted ) , and sublingual temperature . Bacteriological study of the sputum was made at the onset of an exacerbation and 7 , 21 and 35 days afterwards . RESULTS --Of 195 patients enrolled 71 ( 36 % ) contacted their physician for symptoms of an exacerbation . Symptoms improved in all three groups , improvements ranging from 0.54 to 0.75 points per day on a four point scale . PEF% predicted showed improvements in the three groups after the exacerbation , ranging from 0.34 % to 0.78 % predicted per day , finally returning to baseline values . Sublingual temperature did not change . Six of 71 patients consulted their physician because of a relapse between four and 24 days after the start of treatment . In only two of the 50 sputum sample s , collected during an exacerbation , and which contained > or = 10(5 ) bacteria in culture sensitive to the chosen antibiotic given , did any benefit from antimicrobial treatment occur . During the recovery period sputum purulence improved irrespective of antibiotic treatment . CONCLUSIONS --Antibiotics given with a short course of oral prednisolone during an exacerbation do not accelerate recovery as measured by changes in peak flow and symptom scores in ambulatory patients with mild to moderate asthma or COPD when treated by their general practitioners . Moreover , antibiotics do not reduce the number of relapses after treating an exacerbation The aim of the study was to evaluate whether a broad-spectrum penicillin , amoxicillin , was superior to placebo in resolving symptoms of acute exacerbations of chronic bronchitis in patients from general practice . 131 general practitioners included 278 patients over a period of 30 months . The patients were r and omly assigned to treatment with amoxicillin 750 mg b.i.d . or corresponding placebo for 7 days . Patients with pneumonia , a temperature above 38.5 degrees C or heart rate over 100 were excluded for safety reasons . The main effect parameter -- the doctors ' overall evaluation of the treatment -- did not demonstrate any statistically significant difference between amoxicillin or placebo , 63 % versus 64 % of the patients . Resolution of symptoms was obtained by 19 % ( 25/132 ) of the patients in the amoxicillin group compared with 10 % ( 13/136 ) of the patients in the placebo group , P = 0.03 . The present findings do not favour routine use of antibiotics in an attempt to improve the course of acute exacerbations as defined in this study in patients with chronic bronchitis In a double-blind , placebo-controlled trial , patients with acute exacerbations of chronic obstructive pulmonary disease ( COPD ) were r and omly allocated to oral treatment with sparfloxacin ( 200 mg loading dose followed by 100 mg once daily ) or amoxycillin/clavulanic acid ( 500 mg/125 mg tds ) for a total treatment duration of 7 to 14 days . Patients were evaluable if they had a FEV1/FVC ratio of less than 70 % at stable state and presented with a suspected infectious exacerbation defined as increases in dyspnoea , sputum volume and sputum purulence .  The primary efficacy variable was the overall success ( defined as disappearance or improvement of dyspnoea and reductions in sputum volume and purulence ) at end of treatment and follow-up . Overall efficacy was assessed in both the intent-to-treat ( 728 patients ) and the evaluable ( 351 patients ) population s. At the end of treatment and follow-up , success rates were identical for the sparfloxacin ( 87.3 % and 78.7 % ) and amoxycillin-clavulanic acid ( 88.8 % and 79.8 % ) treatment groups . Similar figures were found for the intent-to-treat population . The analysis of drug safety was similar for both treatment groups . The most frequently encountered pathogens were Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis . Sparfloxacin appeared superior for bacteriological eradication of Haemophilus influenzae , and Moraxella catarrhalis . Sparfloxacin in a single daily dose appears at least as effective as  amoxycillin/clavulanic acid  in the treatment of patients with acute exacerbations of COPD 53 patients with planned antibiotic therapy for the treatment of acute exacerbation of chronic bronchitis as an example of a severe bacterial infection requiring antibiotics were included in a prospect i ve , multicentre , double-blind , placebo-controlled study . The chronic bronchitis was staged by forced expiratory volume of the 1st second ( FEV1 ) measured in the infection-free interval prior to the current episode and had to be between 35 and 75 % for the predicted value . Patients were r and omly assigned to receive newer macrolide antibiotics plus either Esberitox ® N or placebo . Antibiotic therapy was administered according to generally accepted guidelines and Esberitox N or placebo was given for 28 days . The baseline-adjusted means for FEV1 ( % ) on day 10 were 68.7 points for the Esberitox N group and 59.2 points for the placebo group ( p = 0.0303 ) . For FEV1 the difference between the two treatment groups was 267 ml ( p = 0.0499 ) . The time to half maximal improvement was 5.7 days in the Esberitox N group compared to 12.8 days in the placebo group . The treatment was well tolerated ; no serious adverse events were documented . In conclusion , comedication of antibiotics with Esberitox N in subjects with acute exacerbation of chronic bronchitis seems to be of benefit for the patient . Apparently , therapy with Esberitox N leads to a faster recovery from this severe bacterial infection , possibly via preventing an impairment of the host ’s immune system which might otherwise occur as a consequence of aggressive antimicrobial therapeutics Abstract A small study of the value of rifampicin and rifamide in chronic bronchitis was undertaken . No reduction of sputum purulence occurred during treatment with either drug . Bacteria resistant to rifampicin emerged rapidly during one week 's treatment . The failure of rifamide appeared to result from low blood-levels and poor tissue penetration . Neither antibiotic should be used in chronic non-tuberculous bronchopulmonary infections Abstract Fifty-two patients with a history of chronic bronchitis and with purulent sputum were treated in a double-blind trial of normal dosage of ampicillin ( 1 g daily ) against higher dosage ( 4 g daily ) and were followed as out- patients for the remainder of the winter season . Patients on the higher dosage responded better than those on the normal dosage , showing less tendency to relapse , longer intervals between relapses , reduced volume of sputum and a more rapid clearance of H. influenzae from the sputum . Unwanted effects were mainly mild , although 3 patients on the higher dosage defaulted because of gastrointestinal disturbances Antimicrobial therapy can have a significant impact in the treatment of acute infectious exacerbations in patients with chronic bronchitis , in whom repeated episodes are common . The aim of this r and omised , double-blind , double-dummy , parallel group study was to compare the efficacy and safety of oral gatifloxacin ( 200 and 400 mg once daily ) administered for 5 days with co-amoxiclav ( 500 mg amoxicillin/125 mg clavulanic acid t.i.d . ) administered for 10 days in 414 adult patients with acute exacerbation of chronic bronchitis .  Overall clinical response rates ( cure plus improvement ) were 86.2 % , 79.4 % and 81.7 % in the gatifloxacin 200 mg , gatifloxacin 400 mg and co-amoxiclav groups , respectively , and the equivalence hypothesis used for statistical analysis showed equivalent efficacy for both gatifloxacin 200 and 400 mg compared to co-amoxiclav . The same was true for rates of bacterial response , with eradication or presumed eradication of causative pathogens achieved in 87.5 % , 87.3 % and 79.1 % of cases in the gatifloxacin 200 mg , gatifloxacin 400 mg and co-amoxiclav groups , respectively . All treatments were well tolerated , with the nature and frequency of treatment-related adverse events similar in all groups . The results of the study show that gatifloxacin is a safe and effective agent for the treatment of patients with chronic bronchitis experiencing an acute infectious exacerbation We conducted a double-blind , r and omized , placebo-controlled trial in 40 patients to evaluate the need for antibiotics in acute exacerbations of chronic bronchitis . All patients were sufficiently ill to require hospitalization although none needed ventilatory support ; the presence of pneumonia was excluded . Treatment consisted of bronchodilators , corticosteroids , and either tetracycline , 500 mg , or placebo by mouth every 6 hours for 1 week . Arterial blood gases , spirometric tests , bacteriologic evaluation of sputum , and patient and physician evaluation of the severity of illness were assessed at the beginning and end of the study . All patients improved both symptomatically and by objective measures of lung function . At the end of the study period there were no differences between those patients receiving tetracycline and those receiving placebo . We conclude that antibiotic therapy is not needed in moderately ill patients with exacerbations of chronic bronchitis Purulent exacerbations of chronic bronchitis are usually treated with antibiotics . Tetracycline , penicillin with strepto mycin , and ampicillin are those most often used . Though innumerable courses of these drugs have been given in this illness , no comparative trial of their efficacy has ever been made ( Stuart-Harris , 1966 ) . We report a r and omized and " blindly " assessed comparison of these antibiotics in hospital in patients , all of whom were moderately or severely ill In the treatment of purulent exacerbations of bronchitis , the usually recommended dose of trimethoprim-sulfamethoxazole ( TMP-SMZ ) was inadequate . Treatment with 480 mg of TMP and 2,400 mg of SMZ daily was very successful . Compared with 2,000 mg of tetracycline hydrochloride daily in a double-blind trial in 197 patients , this dose of TMP-SMZ seemed superior in reducing purulence of the sputum and improving the clinical state of the patient . It was significantly better in preventing deterioration , both during and up to a month after treatment . In the prevention of purulent exacerbations of chronic bronchitis , 40 hospital in patients with advanced chronic bronchitis were given 320 mg of TMP and 1600 mg of SMZ daily for 10 weeks . In a strictly double-blind trial their progress was compared with that of 20 patients given a placebo for 10 weeks . Highly significant clinical and bacteriologic differences favored the patients given chemotherapy .  Side-effects were minimal , and tolerance was excellent . The combination of TMP and SMZ in the above doses should be one of the first choices of chemotherapeutic agents in the treatment and prophylaxis of chronic purulent bronchitis BACKGROUND The role of antibiotics in treatment of patients with moderate exacerbations of chronic obstructive pulmonary disease ( COPD ) is uncertain , but such treatment might be useful in very severe episodes . Our objective was to assess the effects of ofloxacin in patients with exacerbations of COPD who required mechanical ventilation . METHODS We did a prospect i ve , r and omised , double-blind , placebo-controlled trial in 93 patients with acute exacerbation of COPD who required mechanical ventilation . Patients were r and omly assigned to receive oral ofloxacin 400 mg once daily ( n=47 ) or placebo ( 46 ) for 10 days . Primary endpoints were death in hospital and need for an additional course of antibiotics  , both separately and in combination . Analysis was by intention to treat . FINDINGS Three patients dropped out of the study . Two ( 4 % ) patients receiving ofloxacin died in hospital and ten ( 22 % ) did so in the placebo group ( absolute risk reduction 17.5 % , 95 % CI 4.3 - 30.7 , p=0.01 ) . Treatment with ofloxacin significantly reduced the need for additional courses of antibiotics ( 28.4 % , 12.9 - 43.9 , p=0.0006 ) . The combined frequency of death in hospital and need for additional antibiotics was significantly lower in patients assigned to ofloxacin than in those receiving placebo ( 45.9 % , 29.1 - 62.7 , p<0.0001 ) . The duration of mechanical ventilation and hospital stay was significantly shorter in the ofloxacin group than in the placebo group ( absolute difference 4.2 days , 95 % CI 2.5 - 5.9 ; and 9.6 days , 3.4 - 12.8 , respectively ) . INTERPRETATION New fluoroquinolones , such as ofloxacin , are beneficial in the treatment of COPD exacerbation requiring mechanical ventilation Campbell , M. ( 1949 ) . Quart . 7 . Med . , 18 , 379 . ( 1955 ) . Brit . Heart Y. , 17 , 511 . ( 1959 ) . Ibid . , 21 , 65 . ( 1961a ) . Brit . med 7 . , 1 , 691 . ( 1961b ) . Acta Genet . med . ( Roma ) , 10 , 443 . ( 1962 ) . Brit . Heart 7 . , 24 , 625 . ( 1963 ) . Ibid . , 25 , 803 . ( 1966 ) . In A Textbook of Paediatric Cardiology , edited by Hamish Watson . Lloyd-Luke , London . In preparation . and Baylis , J. H. ( 1956 ) . Brit . Heart 7 . , 18 , 475 . and Goodwin , J. F. ( 1965 ) . Progr . cardiovasc . Dis . , 7 , 417 . and Polani , P. E. ( 1961a ) . Lancet , 1 , 463 . ( 1961b ) . Brit . Heart 7 . , 23 , 477 . Carlgren , L.-E. ( 1959 ) . Ibid . , 21 , 40 . Carter , C. 0 . ( 1961 ) . In Conference on Clinical Aspects of Genetics ( 1961 ) , p. 30 . Cockayne , E. A. ( 1938 ) . Quart . 7 . Med . , 7 , 479 . Conference on Clinical Aspects of Genetics held at the Royal College of Phybicians of London ( 1961 ) . Pitman Medical Publishing Co. , Ltd. , London . Edited by F. A. Jones . Conte , W. R. , McCammon , C. S. , and Christie , A. ( 1945 ) . Amer . 7 . Dis . Child . , 70 , 301 . Cox , Diane W. ( 1964 ) . Amer . 7 . hum . Genet . , 16 , 214 . Edwards , J. H. ( 1958 ) . Brit . 7 . prev . soc . Med . , 12 , 115 . Evans , W. ( 1949 ) . Brit Heart 7 . , 11 , 68 . First International Conference on Congenital Malformations , London , 18 - 22 July 1960 . Lippincott , Philadelphia and Montreal , 1961 , and Pitman , London , 1962 . Ford , E. B. , and Huxley , J. S. 1927 . Brit . 7 . exp . Biol . , 5 , 112 . Foxon , G. E. H. ( 1959 ) BIrt . Heart 7 . , 21 , 51 . Fraser , F. C. ( 1959 ) . 7 . chron . Dis . , 10 , 97 . Fuhrmann , W. ( 1958 ) . Z. menshl . Vererb.-u Konstit.-Lehre , 34 , 563 . ( 1961 ) . Acta genet . ( Basel ) , 11 , 289 . ( 1962 ) . Ergebn . inn . Med . Kinderhel ~ k . , 18 , 47 . Gibson , S. , and Lewis , K. C. ( 1952 ) . Amer . 7 . Dis . Child . , 83 , 317 . Harris , L. E. , and Steinberg , A. G. ( 1954 ) . Pediatrics , 14 , 314 . Ingalls , T. H. , Avis . F. R. , Curley , F. J. , and Temin , H. M. ( 1953 ) . 7 . Hered . , 44 , 185 . Kalter , H. ( 1954a ) . Genetics , 39 , 185 . ( 1954b ) . Ibid . , 39 , 975 . and Warkany , J. ( 1957 ) . 7 . exp . Zool . , 136 , 531 . Keith , J. D. , Rowe , R. D. , and Vlad , P. ( 1958 ) . Heart Disease in Infancy and Childhood . MacMillan , New York . Lamy , M. , de Grouchy , J. , and Schweisguth , 0 . ( 1957 ) . Amer . 7 . hum . Genet . , 9 , 17 . L and auer , W. ( 1945 ) . 7 . exp . Zool . , 98 , 1 . ( 1947 ) . Ibid . , 105 , 145 . ( 1952 ) . Ibid . , 120 , 469 . ( 1953 ) . Genetics , 38 , 216 . Lerner , I. M. ( 1954 ) . Genetic Homeostasis . Oliver and Boyd , Edinburgh and London . Lynas . M. A. ( 1958 ) . Ann . hum . Genet . , 22 , 289 . MacArthur , P. ( 1952 ) . Lancet , 2 , 1104 . McIntosh , R. , Merritt , K. K. , Richards , M. R. , Samuels , M. H. , and Bellows , M. T. ( 1954 ) . Pediatrics , 14 , 505 . McKeown T. , MacMahon , B. , and Parsons , C. G. ( 1953 ) . Brit . Heart Z. , 15 , 273 . and Record , R. G. ( 1951 ) . Lancet , 1 , 192 . ( 1960 ) . In Czba Foundation Symposium on Congenital Malformations , edited by G. E. W. Wolstenholme and C. M. O'Connor , p. 5 . Churchill , London . MacMahon , B. ( 1952 ) . Brit . 7 . soc . Med . , 6 , 178 . Mcktown , T. , and Record , R. G. ( 1953 ) . Brit . Heart 7 . , 15 , 121 . Mouquin , M. , Kherumnian , R. , Dur and , M. , Metianu , C. , Moullec ? J. , and Kherumian-Allary , 0 . ( 1956 ) . Bull . Acad . nat . Med . ( Parts ) , 140 , 515 . Neel , J. V. ( 1960 ) . In First International Conference on Congenital Malformations , p. 63 Pare , J. A. P. , Fraser . R. G. , Pirozynski W J. , Shanks , J. A. , and Stubington , D. ( 1961 ) . Amer . 7 . Med . , 31 , 37 . Penrose , L. S. ( 1955 .. Lancet , 2 , 312 . ( 1957 ) Amer . 7 hum . Genet . , 9 , 167 . Polana , P. E. , and Campbell , M. ( 1955 ) . Ann . hum . Genet . , 19 , 209 . -~~~ ( 1960 ) . Ibid . , 24 , 343 . Record , R. G. and Edwards , J. H. ( 1958 ) . Brit . 7 . prev . soc . Med . , 12 , 8 . and McKeown , T. ( 1953 ) . Brit . Heart 7 . , 15 , 376 . Registrar-General ( 1957 ) . Statistical Review of Engl and and Wales for 1957 , Part II , Tables , Civil , Table L. H.M.S.O. , London . Rhodes , A J. ( 1960 ) . In First International Conference on Congenital Malformations , p 106 . Roberts , J. A. F. ( 1953 - 5 ) . Med . 7 . South-West , 70 , 142 . Rutstein , D. D. , Nickerson , R. J. , and Heald , F. P. ( 1952 ) . Amer . 7 . Dis . Chila . , 84 , 199 Seldon , W. A. , Rubinstein , C. , and Fraser , A. A. ( 1962 ) . Brit . Heart 7 . , 24 . 557 . Siller , W G. ( 1958 ) . 7 . Path . Bact . , 76 , 431 . Sorsby , A. ( 1953 ) . Clinical Genetics . Butterworth , London . Stevenson . A C. ( 1957 ) . Amer . 7 . hum . Genet . , 9 , 81 . Taylor , A. I. , and Polani , P. E. ( 1964 ) . Guy 's Hosp . Rep. , 113 , 231 . Tihen . J A. , Charles , D. R. , and Sippel , T. 0 . ( 1948 ) . 7 . Hered . , 39 , 29 Torgersen , J. ( 1946 ) . Acta med . sc and . , 126 , 319 . ( 1950 ) . Amer . 7 . hum . Genet . , 2 , 361 . Trasler , D. G. ( 1958 ) . Genetics and other factors influencing the pathogenesis of  cleft-palate in mice . Ph.D. thesis , McGill Univ . , Montreal . Quoted by Furhmann ( 1962 ) . Uchida . Irene A. , and Rowe , R. D. ( 1957 ) . Amer . 7 . hum . Genet . , 9 , 133 . Warkany , J. -(1960 ) . In First International Conference on Congenital Malformations , p. 99 . Weil . M. H. , and Allenstein , B. J. ( 1961 ) . New Engl . 7 . Med . , 265 , 661 . Wilson , J. G. ( 1959 ) . 7 . chron . Dis . , 10 , 111 . ( 1960 ) . In First International Conference on Congenital Malformations , p. 187 . Roth , C. B. , and Warkany , J. ( 1953 ) . Amer . 7 . Anat . , 92 , 189 . and Wsrkany , J. ( 1949 ) . Ibid .. 85 , 113 . Wood , P. ( 1956 ) . Diseases of the Heart and Circulation , 2nd ed . Eyre and Sinottiswoode , London . Zoethout , H. E. , Bonham Carter , R. E. , and Carter , C. 0 . ( 1964 ) . 7 . med . Genet . , 1 , 2 The anti-inflammatory potential of azithromycin in chronic obstructive pulmonary disease ( COPD ) patients was explored following a st and ard oral dosing regimen . Patients with moderate and severe COPD were treated with azithromycin ( 500 mg , n=16 ) or placebo ( n=8 ) once daily for 3 days in a r and omized , double blind design , to compare effects on inflammation markers with those seen in a previous study in healthy volunteers . A battery of tests was made on serum , blood neutrophils and sputum on days 1 ( baseline ) , 3 , 4 , 11 , 18 and 32 . In comparison to placebo , azithromycin result ed in an early transient increase in serum nitrites plus nitrates ( day 3 ) , associated with a tendency towards an increase in the blood neutrophil oxidative burst to phorbol myristic acetate . Subsequently , prolonged decreases in blood leukocyte and platelet counts , serum acute phase protein ( including C reactive protein ) and soluble E-selectin and blood neutrophil lactoferrin concentrations and a transient decrease in serum interleukin-8 were observed . Blood neutrophil glutathione peroxidase activity showed a prolonged increase after azithromycin treatment . The biphasic facilitatory-then-inhibitory response to azithromycin seen in healthy volunteers is not so clearly detectable in COPD patients , only potential anti-inflammatory effects . Treatment for longer periods may give therapeutic anti-inflammatory benefit in these patients Abstract Pivampicillin is the pivaloyloxymethyl ester of ampicillin but is better absorbed , the absorption pattern being unaffected by food . It was compared with 2 g ampicillin daily using half the equimolar dose , in patients with acute purulent exacerbations of chronic bronchitis . They were r and omly allocated to either treatment , and their response assessed single-blind from clinical , sputum and bacteriological examination . There was no significant difference between the groups , pivampicillin being at least as successful as ampicillin in all assessment s. Both preparations were well tolerated Despite the advances in therapy , chronic obstructive pulmonary disease ( COPD ) requires frequent hospital admissions due to acute exacerbations . We carried out a prospect i ve r and omized study of two groups of patients with COPD , one ( n = 54 ) treated with azithromycin ( 500 mg/day ) for three days every 21 days during the winter months , and a control group ( n = 40 ) without treatment .  A statistically significant reduction in the number of acute infectious episodes ( 187 ) and hospital admissions ( 22 ) was observed in the treated group versus the control group ( 249 and 45 , respectively ) . A short prophylactic treatment course with azithromycin is a good alternative in the management of patients with severe , advanced COPD , and could lead to an improvement in social and healthcare BACKGROUND Clinical trials have not shown a consistent benefit of treating bronchitis with antibiotics . Many physicians , however , treat acute bronchitis with antibiotics because of the possibility of Mycoplasma pneumoniae or other pathogens . The objectives of this study were to determine the effectiveness of erythromycin treatment in patients with acute bronchitis and to determine whether a newly developed rapid M pneumoniae antibody test is useful in predicting which patients will respond to therapy . METHODS We conducted a r and omized , double-blind , placebo-controlled clinical trial at three primary care centers in North Carolina . A convenience sample of 140 patients presenting with acute bronchitis were tested for M pneumoniae , 91 of whom were treated with either erythromycin 250 mg four times daily for 10 days or an identical-appearing placebo . RESULTS Patients treated with erythromycin missed an average of only 0.81 + /- 1.1 days of work compared with 2.16 + /- 3.2 days for placebo-treated patients ( P < .02 ) . There were no significant differences in cough , use of cough medicine , general feeling of well-being , or chest congestion between the erythromycin and placebo groups . Twenty-five percent of the patients tested positive for M pneumoniae . There were no differences in response to erythromycin based on whether the patient had a positive test for M pneumoniae . CONCLUSIONS Erythromycin is effective in significantly reducing lost time from work , but it is not effective in reducing cough or other symptoms in patients with acute bronchitis , regardless of the outcome of the M pneumoniae antibody test UNLABELLED Exacerbations of chronic obstructive pulmonary disease ( COPD ) have an inflammatory component in addition to the possible infectious component . The antiinflammatory properties of fenspiride ( Pneumorel(R ) 80 mg ) should be evaluated in this frequent clinical situation . OBJECTIVES Assess the supplementary therapeutic benefit provided by fenspiride administered in combination with antibiotics in COPD patients presenting an episode of bronchial infection . PATIENTS AND METHODS A preliminary r and omized placebo-controlled double-blind study was conduced in 7 centers . Patients under 80 years of age of both sexes were included . All patients had COPD and presented a bronchial infection defined as the presence of at least 2 of the 3 criteria defined by Anthonisen . Patients were r and omly assigned to group F or group P. Group F received an antibiotic therapy from day 1 to day 11 plus fenspiride ( 3 x 80mg/d from day 0 to day 30 ) . Group P received the same antibiotic therapy plus placebo . Amoxicillin 500 mg plus clavulanic acid 125 , 3 tablets/day , was administered in both groups . RESULTS Thirty-nine patients were included ( group F 19 patients , group P 20 patients ; 6 women and 33 men ; mean age 61.1 + /- 9.8 years ) . The 3 Anthonisen criteria were present in 79 % and 75 % of the patients in group F and P respectively ( NS ) . On day 11 , expectoration resolved in 39 % and 32 % ( NS ) and cough in 44 % and 16 % ( NS ) of the patients in groups F and P respectively . Lung auscultation returned to normal in 83 % of the patients in group F compared with 47 % in group P ( p=0.05 ) . A composite clinical score including expectoration cough and auscultation findings showed that 28 % of the patients in group F were symptom-free on day 11 compared with 0 % in group P ( p=0.04 ) . On day 30 , the two groups were comparable . CONCLUSION In this preliminary study of patients with COPD presenting a bronchial superinfection , there was a significant improvement in lung auscultation and in the composite clinical score in patients given fenspiride . Fenspiride was thus found to provide an early clinical benefit Summary A blind comparison was made of lymecycline , erythromycin , novobiocin and a novobiocin-tetracycline mixture in milder purulent exacerbations of bronchitis occurring in patients treated in hospital .  Lymecycline was marginally superior to the novobiocin-tetracycline mixture , erythromycin was definitely inferior and novobiocin had to be withdrawn because of excessive toxicity Abstract To document the course and prognosis of chronic obstructive lung disease , 200 patients with the disorder were enrolled in a prospect i ve st and ardized study four to eight years ago . Their disease progressed in a more regular and more predictable fashion than had been anticipated from casual clinical observations . Reasonably precise predictions of longevity could be made on the basis of initial findings . Measurements of ventilatory capacity , resting heart rate and carbon dioxide levels were the best indicators of prognosis . Prediction of survival was further improved by consideration of the course of physiologic abnormalities over a two-year follow-up period . Most features of the disease showed a systematic tendency to worsen , but yearly changes were relatively small , often becoming evident only with long-term observation . Data are compatible with the concept that chronic obstructive lung disease is a slowly progressive disorder that begins many years before the onset of clinical symptoms Abstract A comparative study of ampicillin ( 1 g. per day ) , tetracycline hydrochloride ( 1 g. per day ) and methacycline hydrochloride ( 600 mg . or 1 g. per day ) , all given in four divided doses , showed that the four regimens were equally effective in the treatment of infective exacerbations of chronic bronchitis . This conclusion was reached on the basis of serial observations of macroscopic and microscopic sputum purulence , and of the bacterial flora , with special reference to Hœmophilus intluenzœ and Streptococcus pneumoniœ . With all four regimens pus was eliminated from the sputum in an average period of less than four days . This unusually rapid rate of improvement was probably achieved because treatment was started in every case within twenty-four hours of the onset of symptoms . Efficacy and economy can be combined by prescribing the least expensive tetracycline derivative ( at present oxytetracycline ) as soon as the initial symptoms of an infective exacerbation of chronic bronchitis are recognised Abstract In a double-blind study a placebo , tetracycline , and chloramphenicol have been compared in the management of purulent exacerbations of chronic bronchitis . Clinical ly , antibiotic treatment was superior to the placebo . Patients treated with chloramphenicol benefited little more than those given tetracycline , except that chloramphenicol was much better tolerated . Thus antibiotics should be given to most patients who are moderately or severely ill with purulent exacerbations of chronic bronchitis .  Chloramphenicol should be given only after very careful consideration . By a month after treatment the benefits of antibiotics  had largely disappeared The American College of PhysiciansAmerican Society of Internal Medicine ( ACPASIM ) and the American College of Chest Physicians ( ACCP ) developed this evidence -based clinical practice guideline in collaboration . A joint expert panel examined the evidence and developed recommendations . The numbers in square brackets are cross-references to the numbered sections in the accompanying background paper , Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease : A Summary and Appraisal of Published Evidence , which is part 2 of this guideline ( see pages 600 - 620 ) . The guideline and background paper are based primarily on a systematic review compiled in an Agency for Healthcare Research and Policy evidence report prepared by the Evidence -Based Practice Center at Duke University ( 1 ) . Our target audience is primary care physicians and specialists who care for patients with chronic obstructive pulmonary disease ( COPD ) . Although most acute exacerbations of COPD take place and are treated on an outpatient basis , research studies focus on emergency department or inpatient setting s. As a result , this guideline applies to exacerbations treated in those setting s. The guideline presents the available evidence on risk stratification for relapse and 6-month mortality rates , diagnostic testing for acute exacerbations of COPD , and current treatment options for acute exacerbations of COPD . In the United States , 16 million adults have COPD , which accounts annually for 110 000 deaths , more than 16 million office visits , 500 000 hospitalizations , and $ 18 billion in direct health care costs . The disease is characterized by chronic airflow obstruction and episodic increases in dyspnea , cough , and sputum production that are commonly called exacerbations . After an acute exacerbation , most patients experience a transitory or permanent decrease in quality of life , and nearly 50 % of patients discharged from hospitals after acute exacerbations are readmitted more than once in the following 6 months . Therefore , one of the main treatment goals for patients with COPD is reducing the number and severity of annual exacerbations . There is no widely accepted definition of acute exacerbation of COPD , but most published definitions encompass some combination of three clinical findings : worsening dyspnea , increase in sputum purulence , and increase in sputum volume . A severity scale for acute exacerbations developed by Anthonisen and colleagues ( 2 ) is based on these findings as well as others . Type 1 exacerbations ( severe ) have all three clinical findings , and type 2 exacerbations ( moderate ) exhibit two . Type 3 exacerbations ( mild ) have one of these clinical findings plus at least one of the following : an upper respiratory tract infection in the past 5 days , fever without other apparent cause , increased wheezing , increased cough , or a 20 % increase in respiratory rate or heart rate above baseline . We use this scale when referring to severity in this guideline . Acute exacerbations can be triggered by tracheobronchial infections or environmental exposures , and patients often have associated clinical conditions , such as heart failure , extrapulmonary infections , and pulmonary embolism . Therefore , acute exacerbation is mainly a clinical diagnosis . Despite the importance of this disease , the review of the evidence brings to light the paucity of high- quality studies on this subject . Nevertheless , recommendations in this guideline are based on the highest- quality evidence currently available . While the studies of highest quality were often r and omized , controlled clinical trials , these were few in number and tended to enroll small numbers of patients . The clinician must consider this fact when basing management decisions on the guideline recommendations . Current practice s for the diagnosis and management of acute exacerbations of COPD are varied . Some commonly used tests and therapies are not supported by evidence , while others are . The Panel found enough evidence to make recommendations about the use of the following diagnostic and therapeutic methods in acute exacerbations of COPD : chest radiography , acute spirometry , bronchodilators , corticosteroids , antibiotics , oxygen , mucolytic agents , mucus-clearing strategies , and noninvasive positive-pressure ventilation ( NPPV ) .  Indirect evidence shows that arterial blood gases are helpful for determining the present need for oxygen therapy and the potential need for mechanical ventilatory support . We did not find enough evidence to make recommendations regarding the use of pulse oximetry , sputum smear , and culture . Risk Stratification Prediction of Outpatient Relapse All of the studies included for analysis were performed in the emergency department . Relapse was defined as a return visit to the emergency department within 14 days of initial presentation . Identifying patients at high risk for relapse should help guide decisions about hospital admission and follow-up appointments . Several studies have confirmed what most clinicians intuitively know : Patients who have lower baseline FEV1 , low Po 2 , high Pco 2 , and low pH and who receive more bronchodilator  treatments while in the emergency department are more likely to relapse within 14 days of initial presentation . Unfortunately , none of the predictive models perform well enough to justify their uniform use in clinical practice [ 2.1.1 ] . Prediction of 6-Month Mortality The Study to Underst and Prognoses and Preferences for Outcomes and Risks of Treatments ( SUPPORT ) found a 180-day mortality rate of 33 % in its cohort . Significant predictors of 180-day mortality were worse Acute Physiology and Chronic Health Evaluation ( APACHE ) III score , lower body mass index , older age , worse functional status 2 weeks before admission , lower ratio of Po 2 to fraction of inspired oxygen , history of congestive heart failure , lower serum albumin level , and presence of cor pulmonale . Other studies reported similar associations . Although these studies suggest that certain physiologic characteristics are associated with a higher likelihood of inpatient mortality , we conclude that there is currently no reliable method for identifying patients at high risk ( > 90 % ) for inpatient or 6-month mortality . Therefore , these measures should not influence decisions about instituting , continuing , or withdrawing life-sustaining therapies but should prompt a discussion regarding patient preferences for end-of-life care [ 2.1.2 ] . Diagnostic Testing : Chest Radiography and Spirometry Three observational studies showed substantial rates of abnormalities in chest radiography among patients admitted for acute exacerbation of COPD . In one prospect i ve study , which included patients with asthma , chest radiography results prompted change in management in 23.5 % of patients , mostly because of new infiltrates . Observational studies showed that spirometric assessment at presentation or during treatment is not useful in judging severity or guiding management of patients with acute exacerbations of COPD . When measured at the time of an exacerbation , FEV1 showed no significant correlation with Po 2 and only a weak ( although statistically significant ) correlation with Pco 2 . Peak expiratory flow rate is often used in the clinic to approximate FEV1 . One study found a correlation between peak expiratory flow rate and FEV1 . The clinical implication of this finding is not clear , however , because FEV1 is a poor predictor . Despite this fact , many studies use changes in FEV1 as the primary outcome rather than other , more clinical ly pertinent measures ( such as degree of dyspnea or sputum production and quality ) , probably because the latter are much more difficult to quantify and evaluate [ 2.2.2 , 2.2.3 ] . Therapeutic Interventions Bronchodilators Fourteen r and omized trials show that inhaled short-acting 2 agonists , such as albuterol , and anticholinergic bronchodilators , such as  ipratropium  , are equally efficacious in patients with acute exacerbations of COPD . They are also superior to all parenterally administered bronchodilators , including methylxanthines and sympathomimetic agents . Furthermore , some patients may experience additional benefit when a second inhaled bronchodilating agent is administered after the maximal dose of the initial agent is reached . Several studies examined patients receiving a short-acting 2 agonist plus an anticholinergic bronchodilator . In general , patients in these studies had marginally shorter lengths of stay and proportionally larger increases in FEV1 , but hospital admission rates were similar to those of patients receiving one bronchodilator . Since anticholinergic bronchodilators are associated with fewer and milder side effects , it is advisable to start with them and then add a short-acting 2 agonist . Studies are equivocal on the addition of a methylxanthine , such as aminophylline , to inhaled bronchodilators . More important , the potentially serious side effects of the methylxanthines make their use more problematic . In addition , some evidence shows that the efficacy of wet nebulization and dry aerosol delivery systems ( metered-dose inhaler plus a spacer ) are clinical ly equivalent . Therefore , the choice of a specific delivery method should be determined on an individual basis , depending on each patient 's ability to use the different methods ( 3 ) [ 2.3.1 ] . Corticosteroids Six r and omized , placebo-controlled trials showed that for patients hospitalized with acute exacerbation of COPD , systemic corticosteroids given for up to 2 weeks are helpful . Dosage , length of treatment , administration , and setting varied greatly among the studies evaluated . In the largest trial ( Systemic Corticosteroids in Chronic Obstructive Pulmonary Disease Exacerbations ) , patients received a 2-week or 8-week course . The 2-week course consisted of 3 days of intravenous methylprednisolone , 125 mg every 6 hours , followed by oral prednisone for 2 weeks ( 60 mg/d on days 4 to 7 , 40 mg/d on days 8 to 11 , and 20 mg/d on days 12 to 99 hospital patients suffering from acute exacerbations of chronic bronchitis were studied . 50 were treated with tetracycline in a dose of 2 g daily for 10 days , and the results compared with 49
BACKGROUND Most patients with an exacerbation of chronic obstructive pulmonary disease ( COPD ) are treated with antibiotics .
However the value of their use remains uncertain .
Some controlled trials of antibiotics have shown benefit ( Berry 1960 ; Pines 1972 ) while others have not ( Elmes 1965b ; Nicotra 1982 ) .
OBJECTIVES To conduct a systematic review of the literature estimating the value of antibiotics in the management of acute COPD exacerbations .