Management of Acute Bacterial Exacerbations of Chronic Bronchitis: Defining the Role of Moxifloxacin
Harinder S. Malhotra
Caroline M. Perry
The clinical course of chronic bronchitis is intermittently interrupted by acute exacerbations (AECB), especially during the winter months, characterised by an increase in cough, a change in the purulence and volume of sputum, or worsening of dyspnea. Although AECB can be caused by allergens, pollutants, inhaled irritants or viral infections, or by endogenous conditions such as left heart failure, most AECB are precipitated by bacterial infections (ABECB). Patients with chronic bronchitis are estimated to have an average of one to four acute exacerbations per year. The total annual cost of treatment of patients with AECB in the US was calculated to be $US1.2 billion for those aged >=65 years and $US419 million for those aged <65 years (1995 costs). Hospitalization accounted for >95% of these costs. After an acute exacerbation, most patients experience a transitory or permanent decrease in quality of life. It is important that the initial antibacterial therapy is successful as treatment failure can lead to further more costly treatment, especially if hospitalization is required. Thus, treatment regimens that allow patients to be treated successfully as outpatients are likely to be associated with considerable financial benefits. The nontypeable strains of Haemophilus influenzae are the commonest etiological organism for AECB; beta-lactamase-mediated amoxicillin resistance can be expected in 20 to 40% of H. influenzae strains in North America and southern European countries. Strains resistant to trimethoprim, tetracyclines and chloramphenicol are also being increasingly identified. More than 90% of strains of Moraxella catarrhalis, another important etiological agent for AECB, are resistant to amoxicillin in North America and Europe. Streptococcus pneumoniae accounts for about 20% of cases of AECB. During the last three decades, the increase in incidence of S. pneumoniae strains with decreased susceptibility to penicillin has been a serious concern worldwide. Additionally, the use of fluoroquinolones with suboptimal activity against S. pneumoniae (e.g. ciprofloxacin, levofloxacin) has resulted in the appearance of mutations with fluoroquinolone resistance. So it is important that fluoroquinolones used to treat AECB have high levels of activity against S. pneumoniae at clinically achievable serum levels. Moxifloxacin shows good in vitro activity against all of the common pathogens associated with ABECB, such as H. influenzae, S. pneumoniae and M. catarrhalis. Moxifloxacin administered orally, shows good clinical and bacteriological efficacy in the treatment of ABECB. The clinical and bacteriological efficacy of moxifloxacin in the treatment of ABECB was equivalent to that of clarithromycin, azithromycin, levofloxacin and amoxicillin/clavulanic acid in randomized, comparative trials. No strain of the three common organisms responsible for ABECB resistant to moxifloxacin has been detected. Moxifloxacin has also been shown to relieve the symptoms of ABECB more rapidly then azithromycin. In addition, patients with ABECB treated with moxifloxacin have been shown to have better productivity at work than those treated with levofloxacin. Moxifloxacin offers the advantage of once-daily administration and has a low potential for drug interactions. Moreover, dosage adjustment is not required for elderly patients or for those with any degree of renal impairment, or mild or moderate hepatic impairment. The drug is administered as a short, (five day) treatment course and this is likely to be beneficial in terms of patient compliance. Moxifloxacin is generally well tolerated, with most the common adverse event being gastrointestinal disturbance. The drug has been associated with a small degree of prolongation of QTc (mean increase of 6msec). torsade de pointes was reported at a rate of less than 1 per 2 million patient uses. These events occurred in patients with predisposing factors. Conclusions: Moxifloxacin is a broad spectrum antibacterial agent with excellent activity against the common pathogens (including penicillin-resistant S. pneumoniae) involved in ABECB. The drug has a favorable tolerability profile, a low potential for drug interactions and is administered as a convenient once-daily regimen. In addition, it can be used without dosage modification in the elderly and in patients with any degree of renal impairment or mild or moderate hepatic impairment. Moxifloxacin may be considered a good initial option for the treatment of patients with moderate to severe ABECB who are identified to be at risk for treatment failure with current first-line agents and in those who do not respond to initial treatment with other agents.
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