The fluoroquinolone antibacterials have established a firm position in the management of moderate to severe infections, caused by a range of—mostly Gram-negative—pathogens in most of the major organ systems. In some areas (e.g., pyelonephritis, gonorrhoea, enteric fevers, oral management of osteomyelitis, and P. aeruginosa infections), they have become drugs of choice, often replacing parenteral therapy with cephalosporins and aminoglycosides. However, bacterial resistance has appeared not only in predictable species (e.g., staphylo-cocci and P. aeruginosa) but also among organisms (e.g., E. coli) initially thought unlikely to be thus compromised [25,28-32].

Original fluoroquinolones were perceived to be relatively inactive against Gram-positive bacteria, and clinical failures, although in a minority, supported this view. The newer agents—including the 8-methoxyquinolones moxifloxacin and gatifloxacin, together with gemifloxacin—have greatly enhanced anti-pneu-mococcal potency while retaining potency similar to ciprofloxacin against the enterobacteria. Their place in RTI therapy, at a time when burgeoning multiresistance among both pneumococci and H. influenzae increasingly compromises therapy [117], appears ensured. However, quinolone resistance is now being reported and has clear implications for widespread use of the class, notably in sick elderly patients [118]. Considerations of potential cardiac adverse effects in this group [107], however rare, may also influence prescribing.

Other new indications may include extensions to the limited range of pediatric applications, for example, bacterial meningitis, pneumococcal and atypical pneumonias, and suppurative otitis media. These agents also exhibit potency against anaerobes and may, as did trovafloxacin [73], find a major place in intraabdominal and pelvic infection, as monotherapy replacements for cumbersome combinations.

However, the safety of the newest drugs, while established in large prelicensing studies [99-101], is only now being confirmed in uncontrolled populations. The temafloxacin debacle, the abrupt demise of trovafloxacin, and the later withdrawal of grepafloxacin convincingly argue the case for some form of statutory postmarketing surveillance. The newer agents will undoubtedly be used extensively by primary care physicians worldwide, not always appropriately [119]. The effect of the exposure of populations, perhaps including children, to such potent agents, may have at-present-unanticipated ramifications for the epidemiology and etiology of disease. It is hoped that these effects will be positive.

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