Summary
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.
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References
Akalin HE, Unal S, Gur D, Baykal M. Ofloxacin in the treatment of brucellosis. Proceedings of the 3rd International Symposium on Quinolones, Vancouver, Canada, 1990. Abstract 90, 1990
Al-Sibai MB, Halim MA, El-Shaker MM, Khan BA, Qadri SMH. Efficacy of ciprofloxacin for treatment of Bruceila melitensis infections. Antimicrobial Agents and Chemotherapy 36: 150–152, 1992
Andriole VT. Clinical overview of the newer 4-quinolone antibacterial agents. In Andriole (Ed.) The quinolones, pp. 155–200, Academic Press, London, 1988
Baykal M, Akalin HE, Firat M, Serin A. In vitro activity and clinical efficacy of ofloxacin in infections due to Brucella melitensis. Reviews of Infectious Diseases 11 (Suppl. 5): S993–S994, 1989
Bellido F, Pechère JC. Laboratory survey of fluoroquinolone activity. Reviews of Infectious Diseases 11: 5917–5924, 1989
Bergstermann H, Seifert S, Bauer M, Rifai M. Quinolones for mycobacterial diseases. European Journal of Clinical Microbiology and Infectious Diseases (Special Issue): 301–302, 1991
Bernard E, Carles M, Politano S, Laffont C, Dellamonica P. Rickettsiosis caused by Rickettsia conorii: treatment by ofloxacin. Reviews of Infectious Diseases 11 (Suppl. 5): S989–S991, 1989
Bloom BR, Murray CJL. Tuberculosis: commentary on reemergent killer. Science 257: 1055–1064, 1992
Breitschwerdt EB, Davidson MG, Aucoin DP, Levy MG, Szabados NS, et al. Efficacy of chloramphenicol, enrofloxacin and tetracycline for treatment of experimental rocky mountain spotted fever in dogs. Antimicrobial Agents and Chemotherapy 35: 2375–2381, 1991
Butler T, Rumans L, Arnold K. Response of typhoid fever caused by chloramphenicol-susceptible and chloramphenicol-resistant strains of Salmonella typhi to treatment with trimethoprim-sulfamethoxazole. Reviews of Infectious Diseases 2: 551–561, 1982
Cohen ML. Epidemiology of drug resistance: implications for a post antimicrobial era. Science 257: 1050–1055, 1992
Crosby E, Lhosa L, Mirocluesada M, Carrilo C, Gotuzzo E. Hematologic changes in brucellosis. Journal of Infectious Diseases 150: 419–424, 1984
Datta N, Richards H, Datta C. Salmonella typhi in vivo acquires resistance to both chloramphenicol and cotrimoxazole. Lancet 1: 1181–1183, 1981
Ehret J, Judson FN. Susceptibility testing of Chlamydia trachomatis: from eggs to monoclonal antibodies. Antimicrobial Agents and Chemotherapy 32: 1295, 1988
Eykyn SJ, Williams H. Treatment of multiresistant Salmonella typhi with oral ciprofloxacin. Lancet 2: 1407–1408, 1987
Fitzgeorge RB, Featherstone ASR, Baskerville A. The effect of ofloxacin on the intracellular growth of Legionella pneumophila in guinea pig alveolar phagocytes. Journal of Antimicrobial Chemotherapy 22: 53–57, 1988
Franzetti F, Cernushi M, Esposito R, Lazzarin A, Morini M. Ciprofloxacin therapy of Salmonella infections in HIV-infected patients. European Journal of Clinical Microbiology and Infectious Diseases, Special Issue: 404–405, 1991
Furet YX, Deshusses J, Pechère JC. Transport of pefloxacin across the bacterial cytoplasmic membrane in quinolone-susceptible Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 36: 2506–2511, 1992
Garcia-Rodriguez JA, Garcia-Sanchez JE, Trujillano I, Munoz Belido JL. In vitro activity of new quinolones against Bruceila melitensis. Reviews of Infectious Diseases 11 (Suppl. 5): S992–S993, 1989
Garcia-Rodriguez JA, Garcia-Sanchez JE, Trujillano I. Lack of effective bactericidal activity of new quinolones against Brucella spp. Antimicrobial Agents and Chemotherapy 35: 756–759, 1991
Goldstein FW, Chumpitaz JC, Guevara JM, Papadoupoulou B, Acar JF, et al. Plasmid-mediated resistance to multiple antibiotics in Salmonella typhi. Journal of Infectious Diseases 153: 261–265, 1986
Gudiol F, Pallares R, Carratala J, Bolao F, Ariza J, et al. Randomized double-blind evaluation of ciprofloxacin and doxycyclin for Mediterranean spotted fever. Antimicrobial Agents and Chemotherapy 33: 987–988, 1989
Hooton TM, Batteiger BE, Judson FN, Spruance SL, Stamm WE. Ofloxacin versus doxycycline for treatment of cervical infection with Chlamydia trachomatis. Antimicrobial Agents and Chemotherapy 36: 1144–1146, 1992
Hooton TM, Rogers ME, Medina TG, Kuwamura LE, Ewers C, et al. Ciprofloxacin compared with doxycycline for nongonococcal urethritis: ineffectiveness against Chlamydia trachomatis due to relapsing infection. Journal of the American Medical Association 264: 1418–1421, 1990
Jacobs JL, Gold JWM, Murray HW. Salmonella infections in patients with the acquired immunodeficiency syndrome. Annals of Internal Medicine 102: 186–188, 1985
Kojima T, Inoue M, Mitsuhashi S. In vitro activity of AT4140 against clinical bacterial isolates. Antimicrobial Agents and Chemotherapy 33: 1980–1988, 1989
Lang R, Joseph G, Heger B, Diamantstein L, Zweig A, et al. Minimal inhibitory and bactericidal concentrations of five quinolones to clinical isolates of Brucella melitensis. Proceedings of the 3rd International Symposium on Quinolones, Vancouver, Canada, 1990. Abstract 78, 1990a
Lang R, Raz R, Sacks T, Shapiro M. Failure of prolonged treatment with ciprofloxacin in acute brucellosis. Journal of Antimicrobial Chemotherapy 26: 841–846, 1990b
Lang R, Rubinstein E. Quinolones for the treatment of brucellosis. Journal of Antimicrobial Chemotherapy 29: 357–363, 1992
Leysen DC, Haeners A, Pattyn SR. Mycobacteria and the new quinolones. Antimicrobial Agents and Chemotherapy 33: 1–5, 1989
Moulder JW. Comparative biology of intracellular parasitism. Microbiological Reviews 49: 298–337, 1985
Munnich D, Bekesi S. Curing of typhoid carriers by cholecystectomy combined with amoxicillin plus probenecid treatment. Chemotherapy 25: 362–366, 1979
Nakata K, Maeda H, Fujii A, Arakawa S, Umezi K, et al. In vitro and in vivo activities of sparfloxacin, other quinolones and tetracyclines against Chlamydia trachomatis. Antimicrobial Agents and Chemotherapy 36: 188–190, 1992
Olarte J, Galinde E. Salmonella typhi resistant to chloramphenicol, ampicillin and other antimicrobial agents. Antimicrobial Agents and Chemotherapy 4: 597–601, 1973
Perronne C, Gikas A, Tuffot-Pennot C, Grosset J, Vildé JL, et al. Activities of sparfloxacin, azithromycin, temafloxacin and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages. Antimicrobial Agents and Chemotherapy 35: 1356–1359, 1991
Pocidalo JJ. Use of fluoroquinolones for intracellular pathogens. Reviews of Infectious Diseases 11 (Suppl. 5): S979–S984, 1989
Raoult D, Drancourt M. Antimicrobial therapy of rickettsial diseases. Antimicrobial Agents and Chemotherapy 35: 2457–2462, 1991
Raoult D, Zuchelli P, Weiller PJ, Charrel C, San Marco JL, et al. Incidence, clinical observations and risk factors in the severe form of Mediterranean spotted fever among patients admitted to hospital in Marseille 1983–1984. Journal of Infectious Diseases 122: 111–116, 1986
Rastogi N, Goh KS. In vitro activity of the new difluorinated quinolone sparfloxacin (AT-4140) against Mycobacterium tuberculosis compared with activities of ofloxacin and ciprofloxacin. Antimicrobial Agents and Chemotherapy 35: 1933–1936, 1991
Rastogi N, Labrousse V, Goh KS, Carvalho de Sousa JP. Anti-mycobacterical spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages. Antimicrobial Agents and Chemotherapy 35: 2473–2480, 1991
Roca V, Garcia Aguado C, Perez-Cecilia E, Romero J, Gonzalez Lahoz JM, et al. Ciprofloxacin: results of treatment and prevention of relapses of Salmonella spp. bacteremia in HIV-infected patients. 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, October 11–14. Abstract 1533, p. 366, 1992
Ronald AR, Peeling RW. Chlamydial infections and the quinolones. European Journal of Clinical Microbiology and Infectious Diseases 10: 351–354, 1991
Rubinstein E, Potgieter P. Fluoroquinolones in bronchopulmonary infections. International Journal of Antimicrobial Agents, in press, 1993
Ruiz-Beltran R, Herrero Herrers JI. Evaluation of ciprofloxacin and doxycycline in the treatment of Mediterranean spotted fever. European Journal of Clinical Microbiology and Infectious Diseases 11: 427–431, 1992
Scheel O, Reiersen R, Hoel T. Treatment of tularemia with ciprofloxacin. European Journal of Clinical Microbiology and Infectious Diseases 11: 447–451, 1992
Shasha B, Lang R, Rubinstein E. Therapy of experimental murine brucellosis with streptomycin, co-trimoxazole, ciprofloxacin, ofloxacin, pefloxacin, doxycycline and rifampin. Antimicrobial Agents and Chemotherapy 36: 973–976, 1992
Smith JT. Awakening the slumbering potential of the 4-quinolone antibiotics. Pharmaceutical Journal 233: 299–305, 1984
Strand O, Stromberg A. Ciprofloxacin treatment of murine typhus. Scandinavian Journal of Infectious Diseases 22: 503–504, 1990
Syrjälä H, Schildt, R, Räisäinen S. In vitro susceptibility of Francisella tularensis to fluoroquinolones and treatment of tularemia with norfloxacin and ciprofloxacin. European Journal of Clinical Microbiology and Infectious Diseases 10: 68–70, 1991
Track KJ, Collery SV, Smith JA, Beither PJ, Vance J. Ofloxacin in the treatment of sexually transmitted diseases. Reviews of Infectious Diseases 11 (Suppl. 5): 1282–1283, 1989
Trujillo IZ, Quiroz C, Gutierrez MA, Arias J, Renteria M. Fluoroquinolones in the treatment of typhoid fever and the carrier state. European Journal of Clinical Microbiology and Infectious Diseases 10: 334–341, 1991
Tulkens PM. Intracellular distribution and activity of antibiotics. European Journal of Clinical Microbiology and Infectious Diseases 10: 100–106, 1991
Wallace RJ, Bedsole G, Sunter G, Sanders CV, Steele LC, et al. Activities of ciprofloxacin and ofloxacin against rapidly growing mycobacteria with demonstration of acquired resistance following single-drug therapy. Antimicrobial Agents and Chemotherapy 34: 65–70, 1990
Zeiler HJ, Voigt WH. Efficacy of ciprofloxacin in stationary phase bacteria in vivo. American Journal of Medicine 82 (Suppl. 4A): 87–90, 1987
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Pechère, JC. Quinolones in Intracellular Infections. Drugs 45 (Suppl 3), 29–36 (1993). https://doi.org/10.2165/00003495-199300453-00007
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DOI: https://doi.org/10.2165/00003495-199300453-00007