amoxicillin-potassium-clavulanate-combination and Bronchitis--Chronic

Protracted bacterial bronchitis (PBB) is a leading cause of chronic wet cough in children. The current standard treatment in European and American guidelines is 2 weeks of antibiotics, but the optimal duration of therapy is unknown. We describe the first randomised controlled trial to assess the duration of antibiotic treatment in children with chronic wet cough and suspected PBB. We hypothesise that 4 weeks of amoxicillin-clavulanate is superior to 2 weeks for improving clinical outcomes.. Our parallel, double-blind, placebo-controlled, randomised controlled trial was completed in four Australian hospitals. Children aged 2 months to 19 years with chronic (>4 weeks duration) wet cough, and suspected PBB were randomly assigned (1:1) using permuted block randomisation (stratified by age and site) to 4 weeks of amoxicillin-clavulanate (25-35 mg/kg twice daily oral suspension; 4-week group) or 2 weeks of amoxicillin-clavulanate followed by 2 weeks of placebo (2-week group). The children, caregivers, all the study coordinators, and investigators were masked to treatment assignment until data analysis was completed. The primary outcome was clinical cure (cough resolution) by day 28. Secondary outcomes were recurrence of PBB at 6 months, time to next exacerbation, change in Parent-proxy Cough-Specific Quality-of-Life (PC-QoL) score from baseline to day 28 and from day 28 to 7 months, adverse events, nasal swab bacteriology, and antimicrobial resistance. Analyses followed the intention-to-treat principle. This trial is complete and registered with Australian/New Zealand Registry, ACTRN12616001725459.. Between March 8, 2017, and Sept 30, 2019, 106 children were randomly assigned (52 in the 4-week group, median age 2·2 years [IQR 1·3-4·1]; 54 in the 2-week group, median age 1·7 years [1·2-3·8]) with 90 children completing the 4-week treatment. By day 28, the primary endpoint of clinical cure in the 4-week group (32 [62%] of 52 patients) was not significantly different to the 2-week group (38 [70%] of 54 patients; adjusted relative risk 0·87 [95% CI 0·60 to 1·28]; p=0·49). Time to next wet cough exacerbation was significantly longer in the 4-week group than the 2-week group (median 150 days [IQR 38-181] vs 36 days [15-181]; adjusted hazard ratio 0·47 [0·25 to 0·90]; p=0·02). The rate of recurrence of PBB at 6 months was 17 (53%) of 32 patients in the 4-week group vs 28 (74%) of 38 patients in the 2-week group, but the difference between the groups was not significant (adjusted odds ratio 0·39 [0·14 to 1·04]; p=0·07). PC-QoL significantly improved from baseline to day 28 in both groups, but there was no significant difference between them (mean difference in change -0·2 [95% CI -1·0 to 0·6]; p=0·64). From day 28 to 7 months, median PC-QoL remained stable in both groups with no difference in change between them. Data on respiratory pathogens and antimicrobial resistance (paired swabs available for 48 children) were similar between groups. Adverse events occurred in 13 (25%) children in the 2-week group and ten (19%) in the 4-week group (p=0·57).. A 4-week course of amoxicillin-clavulanate for treating children with chronic wet cough and suspected PBB confers little advantage compared with a 2-week course in achieving clinical cure by 28 days. However, as a 4-week duration led to a longer cough-free period, identifying children who would benefit from a longer antibiotic course is a priority.. Queensland Children's Hospital Foundation.

Topics: Amoxicillin-Potassium Clavulanate Combination; Australia; Bronchitis, Chronic; Child; Child, Preschool; Double-Blind Method; Humans; Infant; Quality of Life; Treatment Outcome

To examine study entry microbiology in patients stratified by disease severity in a clinical trial in acute bacterial exacerbation of chronic bronchitis (ABECB).. Patients were assigned to differing antibiotic therapies based on stratification by disease severity using parameters including forced expiratory volume in 1 second (FEV(1)) as a percentage of predicted value, number of exacerbations during the previous 12 months, and defined co-morbidities. All patients were required to have sputum Gram stain and culture at study entry.. There was no statistically significant difference in overall microbiology between patients with less severe and more severe clinical presentations. Typical ABECB pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) were found in 46.2% (147/318) of patients with less severe presentations and 41.9% (143/341) of patients with more severe presentations. Gram-negative organisms and Staphylococcus aureus were also found in both groups. Pneumococcal susceptibilities to the three antibiotics utilized in the trial revealed marked resistance to azithromycin. Limitations of this analysis include that the clinical trial was designed to examine clinical outcomes rather than microbiology, and that we do not correlate study entry microbiology with clinical outcomes.. Stratification of patients by disease severity did not reveal a statistically significant difference in overall microbiological profile. Gram-negative organisms and S. aureus were recovered even from patients with less severe clinical presentations. Pneumococcal resistance varied with the agent tested. These findings may have implications for the selection of appropriate antibiotic therapy.

Topics: Acute Disease; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Bronchitis, Chronic; Double-Blind Method; Drug Resistance, Bacterial; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Ofloxacin; Severity of Illness Index; Sputum

To compare clinical and microbiological efficacy of penicillines and macrolids in patients with exacerbation of chronic bronchitis (CB) basing on long-term follow-up after antibacterial treatment.. Twenty patients with exacerbated CB or chronic obstructive pulmonary disease (COPD) received amoxicillin/clavulanic acid (augmentin) while 20 other patients were given macrolides (sumamed or clacide). Clinical efficacy was assessed by the rate of exacerbation regression and duration of recurrence-free period in the course of 12-month follow-up. Bacteriological examination was conducted 3-5 days, 1 month after the treatment and at recurrent exacerbation.. Patients on augmentin showed faster regression of exacerbation, earlier remission and higher quality of remission than patients on macrolides. Eradication of etiologically significant pathogens on day 3-5 after therapy with augmentin and macrolides was achieved in 92 and 30% patients, respectively, persistence--in 8 and 70%, respectively. Mean duration of remission was 263 +/- 107.1 and 164.9 +/- 112,2 days, respectively. A correlation was found between duration of recurrence-free period and frequency of eradication and persistence of the agents after antibacterial therapy of CB and COPD.. Augmentin promotes a significantly earlier regress of exacerbation symptoms and persistent remission. Eradication potential of augmentin in CB/COPD patients is higher than that of macrolides. Long-term post-exacerbation monitoring (12-month follow-up) discovered that recurrence-free period of augmentin-treated patients is much longer than in patients on macrolides.

Topics: Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bronchitis, Chronic; Female; Humans; Macrolides; Male; Middle Aged; Monitoring, Physiologic; Pulmonary Disease, Chronic Obstructive; Secondary Prevention

This randomized, controlled trial was designed to show that a short, 5-day course of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 mg (Augmentin XR) is as effective clinically as a longer, 7-day course of conventional amoxicillin-clavulanate at 875/125 mg (both given twice daily) in the treatment of acute exacerbations of chronic bronchitis (AECB). Amoxicillin-clavulanate at 2,000/125 mg was designed to extend the therapeutic levels of amoxicillin in serum over the 12-h dosing interval, compared with conventional formulations, to eradicate bacterial strains for which amoxicillin MICs were < or =4 microg/ml while retaining efficacy against beta-lactamase-producing pathogens. A total of 893 patients were randomized and received study medication (amoxicillin-clavulanate at 2,000/125 mg for 443 patients and 875/125 mg for 450 patients). Overall, 141 patients receiving amoxicillin-clavulanate at 2,000/125 mg and 135 receiving the comparator formulation had at least one pathogen identified at screening. Amoxicillin-clavulanate at 2,000/125 mg was as effective clinically in the per-protocol (PP) population at the test of cure (days 14 to 21, primary efficacy endpoint) as amoxicillin-clavulanate at 875/125 mg (clinical success rates of 93.0 and 91.2%, respectively; treatment difference, 1.8; 95% confidence interval [CI], -2.2, 5.7). Bacteriological success in the bacteriology PP population was high for both formulations (amoxicillin-clavulanate at 2,000/125 mg, 76.7%; amoxicillin-clavulanate at 875/125 mg, 73.0%; treatment difference, 3.8; 95% CI, -7.5, 15.0). Both therapies were well tolerated, with a similar incidence of adverse events. Fewer than 5% of patients in each group withdrew from the study due to adverse events. The shorter, 5-day course of amoxicillin-clavulanate at 2,000/125 mg was shown to be as effective clinically as a longer, 7-day course of amoxicillin-clavulanate at 875/125 mg, with high bacteriological efficacy and no difference in tolerability.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Infections; Bronchitis, Chronic; Double-Blind Method; Female; Haemophilus influenzae; Haemophilus parainfluenzae; Humans; Male; Middle Aged; Moraxella catarrhalis; Streptococcus pneumoniae; Treatment Outcome

This is the first prospective clinical trial in which patients with acute bacterial exacerbation of chronic bronchitis have been stratified by degree of underlying illness. Uncomplicated patients were randomised to levofloxacin 750 mg once daily (q.d.) for 3 days or azithromycin q.d. for 5 days. Complicated patients were randomised to levofloxacin 750 mg q.d. for 5 days or amoxicillin 875 mg/clavulanate 125 mg twice daily for 10 days. Regardless of therapy, complicated patients demonstrated lower clinical and microbiological success than uncomplicated patients. Clinical success for clinically evaluable patients was similar for levofloxacin and azithromycin (93.0 versus 90.1%, respectively), and levofloxacin and amoxicillin/clavulanate (79.2 versus 81.7%, respectively). For microbiologically evaluable patients, clinical response to levofloxacin for 3 days was superior to azithromycin for 5 days (96.3 versus 87.4%, respectively), and levofloxacin for 5 days was similar to amoxicillin/clavulanate for 10 days (81.4 versus 80.9%, respectively). Microbiological eradication was superior for levofloxacin for 3 days compared with azithromycin for 5 days (93.8 versus 82.8%, respectively), and similar for levofloxacin and amoxicillin/clavulanate for 10 days (81.4 versus 79.8%, respectively). In conclusion, levofloxacin 750 mg for 3 days was comparable to azithromycin for 5 days for uncomplicated patients with acute bacterial exacerbation of chronic bronchitis, while 5 days of 750 mg levofloxacin was comparable to 10 days of amoxicillin/clavulanate for complicated acute bacterial exacerbation of chronic bronchitis.

Topics: Administration, Oral; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bronchitis, Chronic; Chronic Disease; Cost-Benefit Analysis; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Haemophilus influenzae; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Nausea; Ofloxacin; Patient Selection; Streptococcus pneumoniae; Treatment Outcome

To identify risk factors for late recovery and failure after ambulatory treatment of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD).. Observational, non-randomised study of risk factors carried out in 2001 and 2002 in Primary Care practices. Patients aged 40 or older diagnosed with an exacerbation of CB or COPD of probable bacterial etiology were included in the study and followed up for 10 days. Patients were treated with amoxicillin plus clavulanic acid (co-amoxiclav) 500-125 mg tds for 10 days, clarithromycin 500 mg bd for 10 days or moxifloxacin 400 mg od for 5 days.. Two hundred and fifty-two general practitioners participated, registering 1147 valid patients. The rate of failure at day 10 was 15.1% without significant differences among the antibiotic treatments. Median time to recovery was 5 days. Factors significantly associated with late recovery (>5 days) on multivariate analysis were: use of long-term oxygen (OR=1.96; 95%CI=1.35-2.85); use of short-acting beta-2 agonists (OR=1.51; 1.17-1.92). The use of moxifloxacin had a "protective" effect against late recovery compared to co-amoxiclav (OR=0.34; 0.26-0.45) and clarithromycin (OR=0.41; 0.31-2.85). Factors associated with therapeutic failure were: previous hospitalisation (OR=1.61; 1.08-2.42); and 2 or more exacerbations the previous year (OR=1.51; 1.04-2.17); criteria of CB had a protective effect against failure (OR=0.53; 0.35-0.79).. There are readily identifiable risk factors for ambulatory treatment failure of exacerbations of CB and COPD. In addition, long-term oxygen therapy and short-acting beta-2 agonists are associated with late recovery, and the use of moxifloxacin compared with co-amoxiclav and clarithromycin is associated with faster recovery of symptoms.

Topics: Acute Disease; Adrenergic beta-Agonists; Adult; Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Aza Compounds; Bronchitis, Chronic; Clarithromycin; Drug Therapy, Combination; Epidemiologic Methods; Female; Fluoroquinolones; Humans; Male; Middle Aged; Moxifloxacin; Oxygen Inhalation Therapy; Prognosis; Pulmonary Disease, Chronic Obstructive; Quinolines; Treatment Outcome

In this randomized, non-blinded study, the efficacy and safety of a 5-day course of moxifloxacin (one 400 mg tablet daily) was compared with that of co-amoxiclav (one 625 mg tablet every 8h) for 7 days, for the treatment of acute exacerbations of chronic bronchitis (AECB). A total of 162 patients with clear signs of an acute exacerbation of chronic bronchitis were enrolled. Of these, 153 could be studied. Seventy-nine patients were randomized in the moxifloxacin arm and 74 in the co-amoxiclav arm of the study. The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and ronchi. The success rate in the moxifloxacin group was 88.6% (70 of 79) and that for co-amoxiclav group was 89.2% (66 of 74). At follow-up (28-35 days post-treatment), the continued clinical cure rates were 90.0% (63 of 70) for moxifloxacin and 89.4% (59 of 66) for co-amoxiclav. No significant differences were detected between the two groups. A total of 78 pathogenic bacteria were isolated from the sputum samples of the patients, with Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae being the most frequently isolated pathogens. The eradication rate at 14 days in the valid patients was similar for both groups, 90.9% (20 of 22) for the moxifloxacin group and 90.0% (18 of 20) for the co-amoxiclav group. Both drugs were well tolerated with no differences in the drug-related adverse effects or the patients withdrawing because of an adverse event. These results and the good spectrum of antibacterial activity make moxifloxacin a promising and also safe alternative for the empirical treatment of AECB.

Topics: Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Aza Compounds; Bacteria; Bacterial Infections; Bronchitis, Chronic; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Male; Middle Aged; Moxifloxacin; Quinolines; Sputum; Treatment Outcome

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 randomised, 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.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Infective Agents; Bacteria; Bacterial Infections; Bronchitis, Chronic; Double-Blind Method; Drug Administration Schedule; Female; Fluoroquinolones; Gatifloxacin; Humans; Male; Partial Pressure; Treatment Outcome; Vital Capacity

This randomized, double-blind study evaluated the efficacy and safety of a short, 5-day course of telithromycin, a new ketolide antibacterial, compared with a standard 10-day course of amoxicillin/clavulanate, in the treatment of acute exacerbations of chronic bronchitis (AECB). The study enrolled 325 adult patients with AECB and a history of chronic obstructive pulmonary disease (COPD). Patients received either telithromycin 800 mg once daily (qd) for 5 days (followed by placebo for 5 days) or amoxicillin/clavulanate 500/125 mg three times daily (tid) for 10 days. Clinical cure rates for telithromycin post-therapy (Days 17-21, test-of-cure) and late post-therapy (Days 31-36) were 86.1 and 78.1%, respectively; 82.1 and 75.0% for amoxicillin/clavulanate. Excellent clinical cure rates were also observed for high-risk patients. Bacteriologic outcome was satisfactory for 69.2% of telithromycin recipients vs 70.0% for amoxicillin/clavulanate recipients. Both treatments were generally well tolerated, although the frequency of drug-related adverse events was almost two-fold higher for amoxicillin/clavulanate (25.0 vs. 13.1%). Thus, a 5-day course of telithromycin 800 mg qd is an effective and well-tolerated alternative to a standard 10-day course of amoxicillin/clavulanate 500/125 mg tid for first-line empiric treatment of AECB in adults with COPD.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bronchitis, Chronic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Ketolides; Lung Diseases, Obstructive; Macrolides; Male; Middle Aged; Treatment Outcome

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bronchitis, Chronic; Diagnosis, Differential; Drug Therapy, Combination; Fluoroquinolones; Glucocorticoids; Humans; Practice Guidelines as Topic; Prednisone; Primary Health Care; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bronchitis, Chronic; Drug Therapy; Humans; Macrolides; Meta-Analysis as Topic; Pneumonia; Practice Patterns, Physicians'; Quinolones