Respiratory Infections

The use of fluoroquinolones in respiratory tract infection (RTI) has been under scrutiny since the original reports of clinical failure in, or superinfection during, ciprofloxacin therapy of pneumococcal disease [53]. Thus, despite the reality of predominantly good results in most respiratory syndromes—notably AECBs—the earlier second-generation quinolones were never accepted for use in community-acquired pneumonia (CAP). This also applied to agents such as lomefloxacin and fleroxacin that have MICs for pneumococci in the range of 4 to 16 mg/liter. In contrast, sparfloxacin, grepafloxacin, and trovafloxacin (MIC90s of 0.12-0.5 mg/liter) were fast becoming recognized as potential agents of choice for drug-resistant infections prior to their toxicity-mediated demise [54]. Newer 8-methoxyquinolones such as gatifloxacin and moxifloxacin, which have enhanced anti-pneumococcal potency (MIC90 = 0.12 mg/liter), will undoubtedly inherit the role of preferred drugs as penicillin and macrolide resistance continues to increase and spread. At present, levofloxacin is extensively used, giving clinical response rates of 84-96% after IV-oral switch therapy of CAP and 78-100% in AECBs [54,55]. Moxifloxacin, at present available only as an oral formulation, gives similar results (89-97%), and IV-oral switch regimes using gatifloxacin resulted in response rates of 95-97% [54,55]. New fluoroquinolones may give better results than standard therapy. For example, in CAP IV-oral levofloxacin was superior to IV ceftriaxone-oral cefuroxime [56], and oral trovafloxacin produced superior clinical response rates to amoxicillin [57]. Other measures in CAP may also reflect enhanced outcomes: mortality rates may be significantly decreased [58] and hospital admission rates, ICU admission rates, and length of stay may be reduced [59].

Fluoroquinolones are effective in legionellosis [19] and are now used, alone and in combination, as agents of choice, especially in macrolide failures. The absence of significant interaction with cyclosporin A has advantages compared with macrolide therapy.

Fluoroquinolones are now recommended for acute exacerbations of chronic bronchitis (AECBs) in patients with risk factors for poor outcome by large consensus groups [60], and both moxifloxacin and gatifloxacin give satisfactory short-term clinical outcomes of 89% in AECBs [61,62]. Preliminary data on a direct comparison over 6-month follow-up between gemifloxacin and cla-rithromycin appear to demonstrate a reduction in exacerbations by gemifloxacin therapy compared to clarithromycin that related to failure of pathogen eradication by the latter (data on file, SmithKline Beecham).

Comparison of ciprofloxacin with imipenem in severe pneumonia in hospitalized patients noted a significantly higher clinical response rate with the quinolone and better bacterial eradication rates for the pathogens (predominantly enterobac-teria) pneumococci and P. aeruginosa, although eradication rates for the latter were lower (67 vs. 59% for imipenem) and resistance emerged in 33-53% of isolates [63]. Similar results were obtained with trovafloxacin, while studies of moxifloxacin and gatifloxacin are awaited.

Multidrug-resistant tuberculosis and atypical infections, for example, Myco-bacterium avium complex (MAC), require alternatives to standard therapy, and fluoroquinolones are used widely in combination regimes despite limited efficacy data. Resistance has now been reported in Mycobacterium tuberculosis.

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