Moxifloxacin in Acute Exacerbations of Chronic Bronchitis: Clinical Evaluation and Assessment by Patients

The Journal of International Medical Research 2001; 29: 61 – 73 Moxifloxacin in Acute Exacerbations of Chronic Bronchitis: Clinical Evaluation and As...
Author: Anabel Reed
0 downloads 2 Views 107KB Size
The Journal of International Medical Research 2001; 29: 61 – 73

Moxifloxacin in Acute Exacerbations of Chronic Bronchitis: Clinical Evaluation and Assessment by Patients J LORENZ1, W BUSCH2






Department of Internal Medicine II, Lüdenscheid District Hospital, Germany; 2Bayer Vital GmbH, Leverkusen, Germany; 3BRONCHIMOX (Treatment of Acute Exacerbations of Chronic BRONCHItis with MOXifloxacin) Study Group* *A list of participating investigators and their centres appears in the Appendix

pain and sputum were scored daily by patients. Cough, chest pain and purulent sputum production improved rapidly within the first 5 days of treatment. At least 90% of patients were satisfied with the antibiotic. The clinical success rate (cure and improvement) for all patients involved (intent-to-treat analysis) was 90.5%. The most commonly experienced adverse events were gastrointestinal related, with diarrhoea the most frequent of these (2.7% of all patients).

The clinical success of a 5-day course of oral moxifloxacin (administered once daily at a dose of 400 mg) was evaluated in 328 patients with acute exacerbations of chronic bronchitis (Anthonisen type 1) in a non-comparative study conducted by chest physicians in private practice. Results were assessed on the basis of clinical parameters and, for the first time in a trial involving oral moxifloxacin, by the surrogate marker of patient satisfaction. Improvement in (and severity of) cough, dyspnoea, chest



Antibiotic treatment is indicated in acute


exacerbations of chronic bronchitis (AECB)

Chronic bronchitis is a disease of the lower respiratory tract, characterized mainly by cough and sputum production. According to the World Health Organization (WHO) definition,1 bronchitis is classified as chronic if both cough and sputum production occur for at least 3 months in 2 consecutive years. The incidence of chronic bronchitis in adults is above 10% in Germany,2 which makes it the most common lung disease in the country.

with purulent sputum production, and the benefits of antibiotic therapy over placebo are greatest in the presence of three factors: increased dyspnoea, sputum production and purulent







Moxifloxacin is a new fourth-generation quinolone with significantly improved activity against Gram-positive bacteria and the same


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS

high activity as third-generation quinolones against Gram-negative pathogens. Moxifloxacin also demonstrates increased activity against atypical organisms (Chlamydia, mycoplasma, Legionella) and anaerobes.4,5 The high bactericidal activity of moxifloxacin against Gram-negative and Grampositive organisms helps it to act rapidly. In vitro studies showed that 99% and 99.9% of pneumococci and Haemophilus, respectively, were eliminated after 2 h, and 99.9% of Moraxella after 30 min.6 – 8 Following oral administration, moxifloxacin was found to have linear kinetics over the dose range studied (50 – 800 mg).9 This antibiotic demonstrates an excellent ability to penetrate into the lungs, with high concentrations being obtained in tissues such as bronchial mucosa, epithelial lining fluid (ELF) and alveolar macrophages (1.5 – 2, 6 – 8 and up to 90 times the corresponding average serum concentrations, respectively). Mean concentrations of moxifloxacin (mg/l or mg/kg) in the mucosa (1.0), ELF (3.5) and macrophages (38.6) are far higher than the minimum inhibitory concentrations for pneumococci, Haemophilus and Moraxella, even after 24 h.10 The clinical efficacy of moxifloxacin in respiratory infections has been investigated in over 4000 patients in international, multicentre, double-blind, phase III studies, with a success rate of over 90% being achieved with once-daily oral doses of 400 mg moxifloxacin in all three indications studied (AECB, community-acquired pneumonia and acute sinusitis).11 – 13 The present open, non-comparative study was designed to investigate whether favourable results obtained in controlled clinical trials could also be achieved in community-based practices specializing in chest medicine, and also how patients perceive the treatment outcome.

Not all clinical symptoms of AECB are perceived in the same way by each patient; individuals describe different, specific symptoms as dominating the exacerbation. A rapid improvement in subjective clinical parameters is a therapeutic objective stated in treatment recommendations for patients with chronic obstructive bronchitis and emphysema, published by the German Respiratory League,14 and this objective should be one of the main focuses of treatment. Cough and sputum production are not just important early indicators of chronic bronchitis; the patient considers them to be cardinal symptoms of AECB. In previous clinical trials of AECB treatment, however, little importance has been attached to improving these symptoms and the associated benefits in quality of life. For the first time in this study, various aspects of the effects of AECB on quality of life, based on self-assessment by the patient, were used as secondary criteria of efficacy, in addition to clinical parameters. Data on quality of life were obtained using questions included in a patient-held diary. Some questions needed to be answered each day, over a 12-day observational period. Cough was defined in a precise manner and reported at three different times each day, because of its importance in terms of the stresses caused to the patient.

Patients and methods Fifty-three centres located across Germany participated in the study. The centres were almost exclusively community-based practices specializing in chest medicine.

INCLUSION CRITERIA Patients > 18 years old with chronic bronchitis according to the WHO definition1


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment were eligible for inclusion in the study. It was necessary for the acute exacerbation to be considered bacterial in origin and classified as Anthonisen type 1 (the highest grade, which covers aggravated dyspnoea, increased sputum production and purulence of sputum).

of AECB was assessed and compared with symptoms before the acute exacerbation occurred; wheezing, dyspnoea, cough and amount of sputum were classified as ‘the same’, ‘slightly worse’ or ‘much worse’. Sputum samples were obtained by coughing and assessed on the basis of appearance, i.e. ‘clear’, ‘mucoid’, ‘mucopurulent’ (< 50% pus) or ‘purulent’ (> 50% pus) and colour, i.e. ‘clear’, ‘yellow’, ‘green’ or ‘rust-coloured’. The lung function parameters forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured on days 1, 12 and 28 – 35. Values obtained were compared against age-appropriate reference values and given as a percentage of the reference value. Haematological and biochemical values, including differential blood count, liver enzymes, bilirubin, serum bilirubin, urea and C-reactive protein (CRP), were determined before therapy started. The tests were repeated on day 12 and whenever considered necessary from a medical viewpoint. In general, either a differential blood count or CRP test was considered sufficient. Body temperature (measured under the tongue, under the axilla, rectally or in the ear), blood pressure (Korotkoff V method) and heart rate were also recorded for each patient at every visit.

EXCLUSION CRITERIA Reasons for excluding patients from the study included: known hypersensitivity to moxifloxacin or related substances; treatment with an antibacterial substance within the previous 48 h (except in the case of clear failure to respond to treatment); severe respiratory infections in which parenteral treatment was indicated; severe renal impairment requiring dialysis; severe impairment of liver function; pregnancy or lactation; not using an effective means of contraception; previous participation in this study or participation in another study within the previous 30 days.

ETHICAL CRITERIA The study protocol was approved by the Westphalia-Lippe Ethics Committee and by the 13 regional Ethics Committees accountable for individual investigators. All the patients gave their written consent before entering the study.

STUDY MEDICATION Each patient took one 400-mg moxifloxacin tablet each morning for 5 consecutive days.


A diary containing questions on changes in AECB-related symptoms and on patient satisfaction, designed by the anti-infective and health economics departments of Bayer Vital GmbH, was used for the first time in this study. The diary was given to each patient when they started treatment and some questions were repeated each day.

In accordance with current recommendations, clinical examinations were performed before the start of treatment (day 1), on day 12 (evaluation of success), and between days 28 and 35 (follow-up examination). Each patient underwent a thorough physical examination with particular emphasis on vital functions. Severity of clinical symptoms


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment CHANGES IN SYMPTOMS

quality-of-life assessment will be published separately.

The patient assessment of changes in symptoms of AECB was the main feature of the diary. From the start of treatment to the evaluation of success 12 days later, the patients kept a daily record of what they considered to be the severity and frequency of chest pain and dyspnoea in the previous 24 h; colour and amount of sputum that morning; and the severity of cough ‘all day yesterday’, ‘last night’ and ‘this morning’. Patients assessed each symptom by placing a cross against the appropriate point on a graduated scale. Four categories of severity were considered adequate for chest pain, sputum colour and amount of sputum, there were five categories for dyspnoea, and seven for scoring cough severity (the latter ranging from ‘none’ to ‘unbearable’). A mean score was calculated for questions asked at each of the three daily reference points, to enable the pattern of cough severity to be assessed across the whole patient population. For this purpose, cough severity categories were assigned scores of between 0 (‘none’) and 6 (‘unbearable’). All scores were multiplied by the number of times they were assigned on a specific day, added up and divided by the total number of patients who answered the question.

STUDY CRITERIA The primary endpoint was the evaluation of clinical success (cure or improvement) on day 12. The secondary study criteria were the evaluation of clinical success on day 28 – 35 and the patient assessment of changes in symptoms of AECB.

VALIDITY OF A TREATMENT CYCLE For a treatment cycle to be valid for the per-protocol (PP) analysis of efficacy, the following criteria had to be met: (i) Patient with confirmed acute exacerbation of chronic bronchitis (Anthonisen type 1); (ii) Patient treated with moxifloxacin for at least 4 days in the case of therapeutic success or 3 days in the case of therapeutic failure; (iii) Patient not receiving concomitant therapy with other antibiotics; (iv) No protocol violations which might affect the result of treatment; (v) No essential data missing for the evaluation of the primary study criterion.


The following parameters were used to evaluate clinical success: reduction in respiratory sounds; reduction in dyspnoea; coughing and amount of sputum; improvement in FEV1; normalization of white blood cell count and/or CRP value.

The diary also contained short questionnaires to assess patient satisfaction with the study medication on day 12 and at the follow-up examination (day 28 – 35). The assessment was based on a scale of five categories ranging from ‘extremely satisfied’ to ‘very dissatisfied’. Questions on quality of life were included in the diary. The Nottingham Health Profile, a general quality-of-life questionnaire, was used on the first day of treatment, on day 12 and on day 28 – 35.15 The results of the

SAMPLE SIZE ESTIMATION A cure rate under practice conditions of over 80% was assumed. On this basis, a sample size of 315 patients was calculated in order to obtain a 95% confidence interval for a cure rate, where the difference between lower limit


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment CLINICAL SUCCESS

of the confidence interval and the upper limit of the confidence interval was ≤ 10%.

On day 12, clinical success of treatment was achieved in 297 of 328 patients (90.5%) in the ITT analysis, 5.5% of the patients did not respond and 4% could not be evaluated. According to the PP analysis, clinical success was achieved in 282 of 297 patients (94.9%), 5.1% did not respond. At the follow-up examination between days 28 and 35, the success rates according to the ITT analysis (93.3%) and the PP analysis (93.6%) were almost identical (Table 2). Results of the assessment of AECB symptom severity compared with before the exacerbation, undertaken on days 1, 12 and

Results In total, 328 patients were included in the study, and all were valid for the intent-totreat (ITT) analysis. Thirty-one patients were excluded from the PP analysis owing to protocol violations. The most frequently cited reasons included violations of the inclusion and exclusion criteria (n = 13), essential data missing or invalid (n = 12), or schedule violations (n = 5). The number of patients included in the PP analysis was therefore 297. Demographic data are shown in Table 1.

TABLE 1: Demographic data for the study population Per-protocol


Patients (n)



Age (years)

19 – 88

19 – 88




Body weight (kg)*

80 (± 16)

80 (± 16)

Height (cm)*

170 (± 8)

170 (± 8)

Sex (m/f)



0 – 69

0 – 69



3.3 (± 1.9)

3.3 (± 1.9)


134 (45.1%)

145 (44.3%)


112 (37.7%)

126† (38.6%)

Smokers < 10 cigarettes/day 10 – 20 cigarettes/day > 20 cigarettes/day

51 (17.2%) 6 (11.7%) 44 (86.3%) 1 (2.0%)

56 (17.1%) 6 (10.7%) 49 (87.6%) 1 (1.8%)

Number of cigarettes/day (average)

15 ± 6

15 ± 6

FEV1 before treatment (% of reference value as a median)



Duration of chronic bronchitis since diagnosis (years) Median Number of acute exacerbations in the last 12 months*

*Mean ± SD. †One patient could not be classified as smoker or ex-smoker.


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment

TABLE 2: Clinical cure rates on day 12 and day 28 – 35 in patients with acute exacerbations of chronic bronchitis following treatment with 400 mg moxifloxacin per day for 5 days Day




94.9% (n = 282)

90.5% (n = 297)

28 – 35

93.6% (n = 264)

93.3% (n = 277)

28 – 35, are summarized for the ITT population in Table 3. The frequency of improvement in individual symptoms compared with the

baseline prior to the exacerbation was between 72% and 77% on day 12 and increased again to between 82% and 88% by day 28 – 35. The

TABLE 3: Assessment of severity of clinical symptoms on day 1, day 12 and day 28 – 35 compared with before acute exacerbations of chronic bronchitis (baseline; intent-to-treat analysis)


Day 1 n (%)

Day 12 n (%)

Day 28 – 35 n (%)

Cough Unchanged

4 (1.2)

236 (72.0)

270 (82.3)

Slightly worse

119 (36.3)

70 (21.0)

40 (12.2)

Much worse

205 (62.5)

12 (3.7)

1 (0.3)

10 (3.0)

17 (5.2)

30 (9.1)

253 (77.1)

287 (87.5)

Slightly worse

162 (49.4)

58 (17.7)

21 (6.4)

Much worse

136 (41.5)

7 (2.1)

3 (0.9)

10 (3.0)

17 (5.2)

3 (0.9)

243 (74.1)

274 (83.5)

Slightly worse

170 (51.8)

67 (20.4)

34 (10.4)

Much worse

155 (47.3)

8 (2.4)

3 (0.9)

10 (3.0)

17 (5.2)

2 (0.6)

249 (75.9)

278 (84.8)

Slightly worse

147 (44.8)

59 (18.0)

29 (8.8)

Much worse

179 (54.6)

10 (3.0)

4 (1.2)

10 (3.0)

17 (5.2)

Could not be evaluated

Wheezing Unchanged

Could not be evaluated

Dyspnoea Unchanged

Could not be evaluated

Amount of sputum Unchanged

Could not be evaluated


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment frequency of symptoms classified as ‘worse’ was between 2.1% (wheezing) and 3.7% (cough) on day 12 and 0.3% (cough) and 1.2% (sputum production) on day 28 – 35.

value also decreased from 2.4 ± 4.1 to 0.7 ± 1.1 mg/l (all values for the ITT population).

SAFETY Adverse events classified by the investigator as probably or possibly related to the study medication occurred in 31 patients (9.5%). Over half of these were of a gastrointestinal nature (5.5%), including nine cases of diarrhoea (2.7%), which was the most frequent side-effect, followed by abdominal pain (1.5%) and vomiting (1.2%). Two patients (0.6%) experienced different central nervous system side-effects. The maximum frequency of all other side-effects was also 0.6%. Four patients (1.2%) had to be withdrawn from the study because the medication was poorly tolerated. The causes were vomiting, stomach pains, allergic reaction and palpitations accompanied by anxiety and diarrhoea (one case of each).

LUNG FUNCTION PARAMETERS On day 12, FEV1 values had increased from 64.5% at baseline to 69%, and the FVC value from 75% to 78%, with values either slightly improving or remaining unchanged by day 28 – 35 (in all cases with reference to the median values in the ITT analysis; Fig. 1).

INFLAMMATION PARAMETERS Changes in white blood cell counts and CRP values were used as indicators of inflammatory reaction and response to infection. White blood cell counts were hardly affected by acute exacerbations, therefore there was no significant reduction in the mean value between day 1 (8.7 ± 3.0 × 1000/mm3) and day 12 (8.3 ± 2.8 × 1000/mm3). Where there was an existing shift to the left, however, this regressed under therapy. The percentage of band neutrophils decreased from 4.0 ± 4.3% before treatment to 1.7 ± 1.8% on day 12. The mean CRP




PATIENT ASSESSMENT OF CHANGES IN SYMPTOMS OF AECB All the results based on information recorded in patient diaries relate to the safety or ITT population. The differences between this and

Day 1 Day 12 Day 28 – 35 n = 287 n = 281

80 70

n = 307 n = 295

n = 287

n = 316

60 50



Lung function parameter

FIGURE 1: Changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment patients experiencing frequent or constant chest pain then remained at around 10% until the end of the observational period. At the start of treatment, there were significant differences in cough severity at the three times each day when patients documented this symptom in their diaries. On day 1 the percentage of patients with a cough severity of at least ‘excessive’ was 43% for ‘last night’ compared with 56% for ‘all day yesterday’ and ‘this morning’. This relative difference in severity between day and night persisted throughout the 12-day observational period. The improvement in cough severity followed the same pattern at all times of day. A decrease in cough severity was identifiable from day 1 of treatment, this trend continuing until around day 9. The improvement in cough severity in the first 5 days of antibiotic treatment was noteworthy. The percentage of patients who still had a slight cough increased more rapidly than the percentage of patients with no cough at all, initially, which is illustrated by the distribution of categories of cough severity for ‘last night’ on the 12 days of observation (Fig. 2). The percentage of patients with a cough classified as ‘excessive’ or worse for ‘yesterday’ or ‘this morning’ dropped from 56% on day 1 to 10% on day 12. By day 12, 50% of patients reported no cough at all for ‘last night’, compared with 25% for ‘yesterday’ and ‘this morning’. Changes in the cough score at all three reference times are shown in Fig. 3. The cough score also highlights the rapid improvement in cough severity in the first 5 days of treatment. Almost 90% of the patients were satisfied with the antibiotic they had taken on day 12, this figure increasing to 92% on day 28 – 35. Moreover, > 40% were ‘very’ or ‘extremely’ satisfied. Patient satisfaction scores measured at the follow-up examination

the PP analysis are minimal and are therefore not explicitly mentioned. Averaged out over all the questions, the diary was completed by over 90% of patients. Participation was lower on the first and last day, at 84% and 79%, respectively. Otherwise, the response rate over the period between day 2 and day 11 ranged consistently between 91% and 95%. The only exception to this was the question about sputum colour, where the response rate decreased consistently from 91% on day 5 down to 71% on day 12. The questions on patient satisfaction were answered by > 90% of patients both on day 12 and at the followup examination on day 28 – 35. Dyspnoea showed the slowest improvement. While 6.1% of patients reported that they were not suffering from dyspnoea at the start of therapy, this percentage increased to 21.6% by day 12 (evaluation of success). Even at this point, however, 42% of the patients were still complaining of dyspnoea during everyday activities, when speaking and even at rest. Sputum colour showed a rapid return to normal from day 1 of treatment. Within the first 5 days, the percentage of patients with yellow/green or even brown/blood-coloured sputum fell from 57% to 10%, although this percentage remained relatively constant thereafter. The amount of sputum reported by the patients fell continuously over the whole observational period. The percentage of patients producing more than a tablespoonful of sputum in the morning fell from 30% on day 1 to 8.7% on day 12. In parallel, the percentage of patients producing no sputum increased from 5.4% to 34.6%. The frequency of chest pain decreased significantly in the early days of treatment and 86% of the patients reported little or no chest pain by day 5. The percentage of


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment


Unbearable Very bad Bad Excessive Moderate Slight None

Patients (%)

80 60 40 20 0

1 2 3 4 5 6 7 8 9 10 11 12 Days

FIGURE 2: Changes in cough severity for ‘last night’ under therapy

3.5 Cough severity ‘yesterday’ Cough severity ‘last night’ Cough severity ‘this morning’



2.5 2.0 1.5 1.0 0.5 0.0 1








9 10 11 12

Days FIGURE 3: Mean cough severity score regarding the antibiotic they had taken are represented in Fig. 4.

of treatment with moxifloxacin produced clinical results as good (89%) as 10-day courses with moxifloxacin (91%) or clarithromycin (91%).17 In the present study, the clinical success rate was 90.5% in the overall population and 94.9% in those patients treated in accordance with the protocol, which correlates with response rates found in large multicentre studies conducted under double-blind conditions.13,17 Treatment with moxifloxacin was also well tolerated, as witnessed by the low withdrawal rate. Besides the gastrointestinal effects which are

Discussion The optimum duration of antibiotic therapy for AECB is not known, although existing recommendations are for at least 7 – 10 days of treatment.3,16 Recently, however, there has been a general tendency to shorten treatment durations and acceptable early clinical success rates of around 90% have been achieved with new substances in regimens under 7 days. For example, a 5-day course


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment

Very dissatisfied 1% Extremely satisfied Dissatisfied 7% 7%

Satisfied 49%

Very satisfied 36%

FIGURE 4: Patient satisfaction with the antibiotic on day 28 – 35 (intent-to-treat, n = 297) typically associated with antibiotics, no specific side-effect pattern was identified. Moxifloxacin comes near to the ideal profile of a rapidly and highly effective, welltolerated and easy-to-use antibiotic. A 5-day treatment course is sufficient to produce a cure rate of around 90%. Only one dose strength (400 mg) is required, which can be taken once daily in tablet form, and does not need to be taken with meals. Moxifloxacin does not cause the interactions previously reported with other members of this substance group (e.g. with theophylline).18 The patient assessment of changes in symptoms of AECB and the patient satisfaction questionnaire, used in this study for the first time, were well received by the patients, who were very co-operative about answering the questions. One in two patients classified their cough severity as ‘excessive’ or worse before treatment, which shows the importance of this symptom to the patient. This confirms that it was important to base patient assessments on cough severity in this study. A distressing cough prevents the patient from sleeping, interferes with his/her performance the following day, and can cause social isolation. These factors lead to a deterioration in quality of life. Cough is not one of the Anthonisen criteria, but it seems

reasonable to base evaluations of the efficacy of AECB therapy on improvements in this symptom. The rapid decrease in cough severity following treatment with moxifloxacin is identifiable from the changes in score and the frequency distribution of degrees of symptom severity. This correlates with the rapid improvement in clinical symptoms observed in other studies using this antibiotic. In the present study, although the percentage of patients reporting no cough by day 12 was only 25% or 50% (depending on the time of day), the underlying condition is chronic, and > 60% of the patients enrolled in this study had been diagnosed with chronic bronchitis for ≥ 6 years. Other studies have also shown that some of the symptoms that worsen during AECB, e.g. sputum production and dyspnoea, do not regress to baseline levels for several weeks.19 The percentage of patients reporting no worse than a moderate cough may therefore be more indicative of a return to pre-AECB status. This applied to 90% or 95% of the patients on day 12 of this study (depending on the time of day). The same applies to the cough score, which decreased rapidly in the first 5 days of treatment, but which then levelled out and, although low, hardly changed at all. The mean score for this symptom is necessarily


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment why the effect of treatment on this symptom should be taken into account in future clinical trials. It also enabled treatment to be monitored much more closely than would have been possible by means of medical examinations alone, in this case showing that treatment with 400 mg moxifloxacin once daily produces a very rapid improvement in cough, chest pain and production of purulent sputum. Therapeutic results 1 month after the start of treatment remained as good, evidenced by the clinical success rate of > 93% on day 28 – 35 both in the ITT and the PP analysis. This was supported by the patients, 92% of whom stated that they were satisfied with the antibacterial medication at this point. Both findings confirm indirectly that a 5-day course of treatment with moxifloxacin is effective and justified in AECB. This study shows that moxifloxacin has the same high efficacy in a study designed to simulate practice conditions as has already been observed in randomized, double-blind studies. This study also made it clear, however, that a response rate of > 90% on day 12 does not mean that all the symptoms induced or aggravated by the exacerbation had disappeared. A 5-day course of treatment with moxifloxacin in acute exacerbation of chronic bronchitis produces a high clinical success rate (> 90%) even when used under the conditions of a community-based practice specializing in chest medicine. Important symptoms such as cough and chest pain, which are also distressing for most patients, improve very rapidly under moxifloxacin, probably because of the high antibacterial activity and rapid bactericidal effects of this substance. Moxifloxacin is well tolerated and is associated with a low risk of interaction with other drugs, which makes it

made up of patients with different degrees of cough severity, and this factor should also be considered. Of the other symptoms assessed in the patient diary, chest pain and sputum colour improved in most patients within the first 5 days of treatment with the antibiotic. In line with the literature,19 improvements in dyspnoea and sputum production were much slower. On day 12, ≤ 10% of the patients were still reporting excessive coughing or worse, frequent or constant chest pain, or over one tablespoonful of sputum or sputum darker than white/yellow in colour. Their doctors also documented some symptoms that patients were questioned about. Patients specified the symptoms they had experienced that day or the previous day, but doctors’ assessments reflected the changes in relation to patients’ individual baseline conditions before the onset of AECB. This difference made it difficult to relate symptoms documented by doctors to those documented by patients.

Conclusions The results of this study confirm the efficacy and safety of a 5-day course of treatment with 400 mg moxifloxacin once daily in patients with AECB. The success rate, in the opinion of the investigators, correlated well with the level of satisfaction with the antibacterial treatment among the patients: both were above 90%. As a surrogate parameter incorporating both the improvement in symptoms perceived by the individual and the tolerability of the antibiotic, the satisfaction score is the parameter which most accurately reflects the overall verdict of the patient. The daily documentation of the main symptoms in the form of self-assessment by patients first and foremost highlighted the impact of cough on quality of life, which is


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment easy to use in daily practice. The rapid relief from cough and other symptoms is clearly appreciated by the patient. Rapid efficacy and tolerability together lead to a high level of patient satisfaction with this treatment.

Darmstadt; H Görner, Bad Freienwalde; H-J Graf, Cologne; K Harzbecker, Aue i Sachsen; A Heye, Wuppertal; H-P Hlawa, Altenburg; R Hütling, Minden; J-P Jacobsen, Ahrensburg; F Karmann, Fürstenfeldbruck; A Koch, Zell i W; B Kroemer, Kaufbeuren; B Kuhr, Langenhagen; R Laumen, Fulda; G Lehmann, Fuldatal; L Leonhardt, Hanover; K Liebscher, Rostock; J Lorenz, Lüdenscheid; R Luther, Magdeburg; S Molitor, Hanover; M Möller, Hanau; N Mülleneisen, Leverkusen; B Randerath, Osnabrück; D Raps, Schopfheim; S Regan, Hanover; W Reier, Bochum; G Reiner, Fürstenfeldbruck; J Rumpf, Hof/Saale; V Schlegel, Teuchern; C Schöning, Brunsbüttel; D Schuster, Wiesbaden; H Schwarting, Kiel; U Steinhauser, Sinsheim; K-O Steinmetz, Darmstadt; G Stöckle, Heilbronn; P Stutz, Bonn; BG Trümper, Erfurt; L Volgmann, Hanover; B Waberzeck, Hartha; G Walther, Auerbach/Vogtland; H Weber, Augsburg; K-H Winterstein, Königs Wusterhausen; W Zachgo, Geesthacht; TH Zahn, Ansbach.

Acknowledgement This paper has been translated into English and adapted from a paper first published in Germany.20

Appendix INVESTIGATORS (AND THEIR CENTRES) PARTICIPATING IN THE BRONCHIMOX STUDY GROUP, GERMANY B Askar, Berlin; A Bisping-Arnold, Freising; K Böge, Steinhagen; H Bönecke, Lienen; O-J Brückner, Munich; E Chesin, Frankfurt/Oder; R Deckelmann, Leipzig; W Dettweiler, Reutlingen; R Dichmann, Witten; G Eckardt, Leipzig; J-G Eckhard, Rüsselsheim; F Elling, Augsburg; H Evers, Beelitz; U Felgner, Oranienburg; H-W Fischer, Verden; H Fleck,

• Received for publication 28 September 2000 • Accepted 14 January 2001 ©2001 Cambridge Medical Publications

References 1 American Thoracic Society: Definitions and classification of chronic bronchitis, asthma and pulmonary emphysema. Am Rev Resp Dis 1962; 85: 762 – 768. 2 Nolte D: Epidemiologie. In: Bronchitis. Urban & Schwarzenberg (Konietzko N, ed). Munich: Urban and Schwarzenberg, 1995; pp37 – 51. 3 Anthonisen NR, Manfreda J, Warren CPW, Hershfeld ES, Harding GK, Nelson NA: Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 1987; 106: 196 – 204. 4 Bauernfeind A: Antibiotic susceptibility patterns of respiratory isolates of Klebsiella pneumoniae in Europe and the USA in 1992 and 1993. The Alexander Project Collaborative Group. J Antimicrob Chemother 1996; 38: (Suppl A): 107 – 115. 5 Dalhoff A, Petersen U, Endermann R: In vitro

activity of BAY 12-8039, a new 8methoxyquinolone. Chemotherapy 1996; 42: 410 – 425. 6 Boswell FJ, Andrews JM, Wise R, Dalhoff A: Bactericidal properties of moxifloxacin and post-antibiotic effect. J Antimicrob Chemother 1999; 43 (Suppl B): 43 – 49. 7 Dalhoff A: Pharmacodynamics of fluoroquinolones. J Antimicrob Chemother 1999; 43 (Suppl B): 51 – 59. 8 Wiedemann B: Pharmacodynamic activity of moxifloxacin in an in vitro model against Gram-positive and Gram-negative pathogens (Abstract). 8th International Congress on Infectious Diseases, Boston, USA, 1998. 9 Stass H, Kubitza D: Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man. J Antimicrob Chemother 1999; 43 (Suppl B): 83 – 90. 10 Andrews J, Honeybourne D, Jevons G, Wise R:


J Lorenz, W Busch, I-M Thate-Waschke et al. Moxifloxacin in AECB: evaluation and assessment

Penetration of BAY 12-8039 into bronchial mucosa, epithelial lining fluid and alveolar macrophages following a single 400 mg oral dose (Abstract). 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego, USA, 1998. 11 Burke T, Villanueva C, Mariano H, Huck W, Orchard D, Haverstock D, et al: Comparison of moxifloxacin and cefuroxim axetil in the treatment of acute maxillary sinusitis. The Sinusitis Infection Study Group. Clin Ther 1999; 21: 1664 – 1677. 12 Fogarty C, Grossman C, Williams J, Haverstock D, Church D, for the Community-Acquired Pneumonia Study Group: Efficacy and safety of moxifloxacin vs clarithromycin for community-acquired pneumonia. Infect Med 1999; 16: 748 – 763. 13 Wilson R, Kubin R, Ballin I, Depperman KM, Baaris HP, Leophonte P, et al: Five day moxifloxacin therapy compared with 7 day clarithromycin therapy for the treatment of acute exacerbations of chronic bronchitis. J Antimicrob Chemother 1999; 44: 501 – 513. 14 Wettengel R, Bohning W, Cegla U, Criee C, Fichter J, Geisler L, et al: Empfehlungen der

Deutschen Atemwegsliga zur Behandlung von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem. Med Klein 1995; 90: 3 – 7. 15 Hunt SM, McEwen J, McKenna SP: Measuring health status: a new tool for clinicians and epidemiologists. J R Coll Gen Pract 1985; 4: 185 – 188. 16 Vogel F, Worth H, Adam D, Elies W, Ewig S, Höffken G, et al: Rationale Therapie bakterieller Atemwegsinfektionen. Chemother 2000; 9: 3 – 23. 17 Chodosh S, DeAbate CA, Haverstock D, Aneiro L, Church D: Short-course moxifloxacin therapy for the treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group: Respir Med 2000; 94: 18 – 27. 18 Wijnands JA, Vree TB: Interaction between the fluoroquinolones and the bronchodilator theophylline. J Antimicrob Chemother 1988; 22 (Suppl C): 109 – 114. 19 Grossmann RF: Defining the problem: acute exacerbations of chronic bronchitis. Infect Med 1998; 15 (Suppl E): 20 – 25. 20 Lorenz J, Busch W, Thate-Waschke I-M, für die BRONCHIMOX-Studiengruppe: Moxifloxacin bei akuter Exazerbation der chronischen Bronchitis. MMW Fortschr Med 2000; 142: 63 – 70.

Address for correspondence Professor Dr Med J Lorenz Innere Abteilung II, Kreiskrankenhaus Lüdenscheid, Paulmannshöherstraße 14, D-58505 Lüdenscheid, Germany.


Suggest Documents