Acute Exacerbations of Chronic Bronchitis

Abstract

Acute exacerbations of chronic bronchitis (AECB) are a major cause of morbidity and mortality. Bacterial pathogens are implicated in about half the episodes of AECB. Empirical antibacterials have a significant benefit in AECB; however, several recent developments have considerably complicated antibacterial choice for this condition. New fluoroquinolone antibacterials introduced in the last decade are theoretically well suited for the treatment of AECB, as the in vitro antimicrobial spectrum of these drugs includes all the major pathogens involved. The pharmacokinetic and pharmacodynamic properties of the new fluoroquinolones are superior to many other antibacterials used to treat AECB. In trials, clinical success with the new fluoroquinolones was equivalent and bacteriological success was occasionally superior to nonfluoroquinolone comparators. However, these clinical trials did not assess several potentially important end-points for which the theoretical superiority of the fluoroquinolones may translate into differences in outcome. Rare but serious adverse effects with some of the new fluoroquinolones have shaken the confidence of prescribing physicians in this class of drugs. Emergence of the resistance of Streptococcus pneumoniae to fluoroquinolones has raised concerns about indiscriminate and widespread use of the new agents for trivial infections. Patients with AECB are a heterogeneous population who should be stratified in order to appropriately choose empirical antibacterial therapy. Highly efficacious antibacterial therapy, such as the new fluoroquinolones, is appropriate as a first-line choice for patients who have risk factors for a poor outcome or are in intensive care units. Such selected use of the new fluoroquinolones balances individual benefit with societal concerns of the use of these agents for AECB.

Newer fluoroquinolones in the treatment of acute exacerbations of COPD

“…Newer fluoroquinolones are less susceptible to efflux. It appears that more than one mutation is needed for significant resistance to the newer fluoroquinolones to develop (Obaji and Sethi 2001). Resistance to older fluoroquinolones such as ciprofloxacin or levofloxacin is more likely to occur and this in turn translates into partial resistance to newer fluoroquinolones such as moxifloxacin.…”

“…Thus it may be preferable to use newer fluoroquinolones rather than the older classes for respiratory tract infections which require the antibiotic to cover all common respiratory pathogens including the pneumococcus. Drugs such as moxifloxacin with its favorable pharmacokinetic and pharmacodynamic properties allied with the above could, it is argued, delay the emergence of significant resistance (Obaji and Sethi 2001; Sethi 2005). …”

“…Their prolonged half-lives allow once-daily administration which should have a positive benefit on compliance. The cytochrome p450 system in the liver is not extensively involved in the metabolism of the newer fluoroquinolones thus decreasing potential for drug–drug interactions (Obaji and Sethi 2001). The extent and rate of absorption may be reduced by cations such as magnesium, aluminium, or iron products (commonly found in antacids) which bind the antibiotic.…”

“…There is concern over resistance developing if the drugs are used to treat common conditions, their side-effects, and the perceived lack of superiority over comparators (Obaji and Sethi 2001; Sethi 2005; Wilson 2005). Antibiotics should be used judiciously during COPD exacerbations and guidelines have highlighted purulent sputum, disease severity, and comorbid illness as important factors when making the decision.…”

Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success

“…The first generation of fluoroquinolones, such as ofloxacin and ciprofloxacin, preferentially targets one of the two loci. Since 1994, however, a number of newer ''dual-activity'' fluoroquinolones, including levofloxacin (the second generation) and gatifloxacin and moxifloxacin (the third generation) (14), that demonstrate more comparable activity against both genes, have been developed. Because at least two mutations are usually required in order to confer a biologically significant resistance to these newer agents, the likelihood for a resistant strain to emerge during treatment of a fully susceptible infection is much lower (15)(16)(17).…”