Quinolones in intracellular infections.

Intracellular parasites are those which spend most of their lives within host cells. The fluoroquinolones demonstrate favourable intracellular pharmacokinetics for the treatment of intracellular infections; these agents diffuse and accumulate in the phagocytes, mainly in the cytosol, and do not associate with cellular organelles. The fluoroquinolones are generally active against Salmonella spp. in vitro, and have been used successfully in the treatment of typhoid fever, Salmonella bacteraemia in patients with AIDS, and chronic enteric carriage. Fluoroquinolone monotherapy has also been found satisfactory in the treatment of tularaemia and Mediterranean spotted fever. Quinolones, alone or in combination with other agents, have also shown promise in animal models of legionellosis and in limited clinical studies. Quinolones, particularly ciprofloxacin and ofloxacin, have notable antimycobacterial activity. Both agents have been used in combination with other antimycobacterial drugs in the treatment of infections caused by Mycobacterium tuberculosis, M. avium-intracellulare complex, rapidly growing mycobacteria and M. leprae, and deserve consideration as part of a multi-drug regimen in otherwise untreatable mycobacterial infections. Clinical data regarding fluoroquinolone monotherapy in brucellosis indicate unacceptable failure rates which preclude the use of these agents in this indication. The quinolones have some efficacy in genital chlamydial infections, but may have limitations in this indication also. In conclusion, as a result of the in vitro activity of the quinolones and their favourable pharmacokinetics, these agents are now an important part of the armamentarium against intracellular infections.

Newly documented antimicrobial activity of quinolones.

The improved antimicrobial activity of newer fluoroquinolones and novel applications recently found for the drugs already marketed are reviewed. Several new compounds are more active against gram-positive bacteria than the presently marketed fluoroquinolones. WIN 57273, the most potent compound in vitro on a weight basis, is 16 to 128 times more active than ciprofloxacin against various staphylococci, streptococci, Enterococcus spp., Corynebacterium spp., Listeria monocytogenes and Bacillus spp. BMY 40062, PD 117558, PD 127391, sparfloxacin, temafloxacin and tosufloxacin also show enhanced in vitro efficacy against these species. These drugs also possess increased activity against various anaerobes, notably Clostridium perfringens, Clostridium difficile and the Bacteroides fragilis group. Mycobacterium tuberculosis, rapidly growing mycobacteria other than Mycobacterium chelonae, and Mycobacterium leprae are often susceptible to quinolones displaying bactericidal activity which is potentially useful for curing difficult-to-treat mycobacteriosis. In addition, a number of new products, notably those containing a cyclopropyl group, are more active than reference fluoroquinolones against Mycobacterium leprae. Sparfloxacin, BMY 40062 and WIN 57273 compare favorably with older fluoroquinolones in the killing of intracellular Legionella spp., and several of the newer compounds have greater antichlamydial potency. Improved antibacterial activity has also been found against Mycoplasma hominis, Ureaplasma urealyticum, Acinetobacter spp. and Pseudomonas maltophilia. By contrast, the newer quinolones have similar or less activity against Pseudomonas aeruginosa and Enterobacteriaceae. Recently, pefloxacin, ofloxacin and ciprofloxacin were found to be active against protozoa, including Plasmodium spp., Trypanosoma cruzi and Leishmania donovani, but not against Toxoplasma gondii. In the near future, more specific research testing unusual pathogens may lead to the identification of quinolones with more selective activity.