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Journal of Antimicrobial Chemotherapy (1996) 37, 491-500
© 1996 The British Society for Antimicrobial Chemotherapy

research-article

Comparison of the activity of fluoroquinolones against Mycobacterium avium in cell-free systems and a human monocyte in-vitro infection model

Hiroe Shiratsuchia,*, Michael R. Jacobsa, Anthony J. Pearsonb, Nandagopal Venkataprasada, Gilles Klopmanb and Jerrold Ellnera

aDepartment of Medicine, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA bChemistry Department, School of Medicine and Case Western Reserv University Cleveland, Ohia 44106, USA

Received 12 April 1995; returned 31 August 1995; accepted 27 October 1995

*Corresponding author: Dr Hiroe Shiratsuchi, Division of Infectious Diseases, Case Western Reserve University School of Medicine, 10th Floor West, Biomedical Research Building, 10900 Euclid Avenue, Cleveland, Ohio 44106-4984, USA

Mycobacterium avium frequently causes disseminated infection in advanced AIDS. Some quinolones including ciprofloxacin and sparfloxacin have anti-M. avium activity in cell-free systems in vitro. Acidic conditions within macrophages and variable intracellular drug penetration and compartmentalization may, however, alter the susceptibility of M. avium to these antimicrobial agents in human tissues. We, therefore, tested the activities of 47 quinolones against M. avium in a human monocyte infection model using ciprofloxacin susceptible (MIC = 0.25 mg/L) and resistant (MIC = 4 mg/L) patient isolates. Monocytes from healthy subjects were infected with M. avium and cultured with or without antimicrobials for 8 days. Some quinolones had poor activity against M. avium in the monocyte culture system despite low MICs (≤0.25 mg/L); in contrast, some quinolones with MICs > 32 mg/L showed some inhibition of M. avium growth within monocytes at 4 mg/L. Six quinolones synthesized based on structure-activity analysis were more active than ciprofloxacin. These data underscore the importance of evaluating drug activity of new antimicrobial agents against intracellular pathogens in a macrophage model as well as in cell-free systems.


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S. J. Bounds, R. Nakkula, and J. D. Walters
Fluoroquinolone Transport by Human Monocytes: Characterization and Comparison to Other Cells of Myeloid Lineage
Antimicrob. Agents Chemother., October 1, 2000; 44(10): 2609 - 2614.
[Abstract] [Full Text]


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