Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages

Perronne, C.; Gikas, Achille; Truffot-Pernot, C.; Grosset, J; Vildé, J. L.; Pocidalo, J J

doi:10.1128/aac.35.7.1356

Cited by 83 publications

(40 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MO-1 strain of MAC, used in our previous studies (2,(8)(9)(10)(11)(12), was isolated from a patient with AIDS and used after a single subculture on mycobacterial Middlebrook 7H11 agar (Difco Laboratories, Detroit, Mich.) supplemented with Middlebrook OADC enrichment (Difco). One flat transparent colony was picked and cultivated at 37ЊC in Middlebrook 7H9 broth (Difco) supplemented with ADC enrichment (Difco) in Falcon tissue culture flasks (Becton Dickinson, Oxnard, Calif.).…”

Section: Methodsmentioning

confidence: 99%

Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity

Cohen

Perronne

Lazard

et al. 1995

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Several murine models have been used to evaluate the activities of antimicrobial agents against Mycobacterium avium infection. The main model used is the beige mouse model, but beige mice are expensive and not easily available. Thus, we developed a model of infection in wild C57BL/6 mice. The drugs that exhibited some activity in a previous model of early infection were evaluated in a new model of established infection. Sparfloxacin (50 mg/kg of body weight), ethambutol (50 mg/kg), minocycline (25 mg/kg), and the inhibitor of the cortisol receptors RU-40555 (100 mg/kg) were compared with clarithromycin (50 mg/kg). Treatments were started 5 weeks after the inoculation and were continued for 21 days. Sparfloxacin and RU-40555, which exhibited a moderate activity in the model of early infection, were not effective in this model of established infection. Clarithromycin and combinations with clarithromycin kept their activities against M. avium infection, both in the spleen and in lungs. The present model of established infection of normal C57BL/6 mice is more relevant than the model of early infection for a stringent evaluation of drugs.Disseminated Mycobacterium avium complex (MAC) infection is one of the most common bacterial infections in patients with AIDS (7). The experimental evaluation of the activities of antimicrobial agents against MAC is done in cellular models using macrophages or in animal models. The main animal model used is the beige mouse model (1,5). This model uses mice that are deficient in natural killer cells, providing a kind of immunodeficiency different from that of AIDS in humans. Beige mice, which often develop spontaneous tumors, are expensive and not easily available. Alternative models of mice with cellular immunodeficiency, such as TxCD4 Ϫ mice, Thxb mice, or nude mice, have been suggested (3, 4). TxCD4 Ϫ mice are C57BL/6 mice thymectomized at 4 weeks of age and treated intravenously with anti-CD4 antibodies. Thxb mice are adult thymectomized BALB/c mice that are subjected to lethal whole-body gamma irradiation and are reconstituted with syngeneic bone marrow cells. Nude mice require a sterile environment. These models, difficult to realize, are not easily used for routine investigations. We have shown that the CFU counts of MAC in organs of untreated wild C57BL/6 mice progressively rose after an initial 4-week plateau (10). The bacterial load reaches concentrations higher than 10 8 CFU/g of spleen and higher than 10 7 CFU/g of lung after 6 months of infection, without the spontaneous clearance of bacteria observed with Swiss Webster mice (4-6). The model of early infection of normal C57BL/6 mice may be used for a rapid screening of drugs (8,9,10). In patients with AIDS, MAC infection has a subacute or a chronic clinical course. Thus, a model of established infection of C57BL/6 mice should be more relevant than the model of early infection for mimicking human infection and should represent a more stringent model for the evaluation of antimicrobial agents.Clarithromycin is now considere...

show abstract

Section: Methodsmentioning

confidence: 99%

Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity

Cohen

Perronne

Lazard

et al. 1995

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…6 SFX has been reported to be more active in vitro than other quinolones against some microorganisms, including staphylococci and mycobacteria. [7][8][9] GFX is an advanced generation of fluoroquinolones that offers several advantages over previous agents, including enhanced in vitro activity against clinically important pathogens and improved pharmacokinetics.…”

mentioning

confidence: 99%

Validated Polarographic Methods for the Determination of Certain Antibacterial Drugs

2007

View full text Add to dashboard Cite

“…Among new macrolides, clarithromycin was reported to exhibit a good activity against M. avium complex in human macrophages (15,16), in the beige-mouse model of M. avium complex infection (8,12), and in the blood of patients with AIDS, in which it decreases bacterial counts (6).…”

mentioning

confidence: 99%

Activities of WIN-57273, minocycline, clarithromycin, and 14-hydroxy-clarithromycin against Mycobacterium avium complex in human macrophages

Cohen

Perronne

Truffot-Pernot

et al. 1992

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

The activities of the fluoroquinolone WIN-57273, 14-OH clarithromycin (a human metabolite of clarithromycin), and minocycline against two virulent strains of Mycobacteium avium complex were evaluated in a model of intracellular infection and compared with that of clarithromycin. Human monocyte-derived macrophages were infected at day 6 of culture. Intracellular CFU at 60 min and intracellular and supernatant CFU on days 4 and 7 were counted after inoculation. The concentrations used, which were equal to peak levels in serum, were 3 pLg of WIN-57273 per ml (MICs for the two strains, 1 a.g/ml), 4 mg of 14-OH clarithromycin per ml (MICs, 8 and 2 Fg/ml, respectively, at pH 7.4), 4 ,g of minocycline per ml (MICs, 64 and 32 Fg/ml, respectively), and 4 ag of clarithromycin per ml (MICs, 2 and 0.5 ILg/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN-57273, minocycline (P < 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P < 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P < 0.02), clarithromycin (P < 0.02), 14-OH darithromycin plus darithromycin (P < 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14-OH darithromycin (P < 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than carithromycin against strain MO-1 (P < 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P < 0.02) was more effective than clarithromycin alone against strain LV-2. Thus, clarithromycin plus minocycline, which corresponds in humans to three active molecules, may exhibit a better efficacy than clarithromycin in this model.Mycobacterium avium complex, a primarily intracellular bacterium which multiplies within phagocytic cells, frequently causes infection in patients with AIDS (7,20 (14). Minocycline is a longer-acting tetracycline derivative whose in vitro activity against M. avium complex was reported by Tsukamura in 1980 (18). Recently, in view of the high activity of a clarithromycin and minocycline combination against Mycobacterium leprae (13), it seemed interesting to test the activity of this combination against M. avium complex. In patients with AIDS treated with clarithromycin (2 g/day), the peak level of clarithromycin in serum was accompanied by a very similar concentration of 14-hydroxy-clarithromycin (1, * Corresponding author. 4). This human metabolite has a longer half-life than clarithromycin, and its trough level is higher than that of clarithromycin. Thus, 14-OH clarithromycin could participate in the therapeutic efficacy of clarithromycin in humans. The efficacy of this metabolite, which is not present in mice, cannot be assessed by clarithromycin treatment of infected mice.The aim of the present study was to evaluate, in a cell model, the activities of WIN-57273, minocycline, 14-OH clarithromycin alone, and 14-OH clarithromycin in combination with other drugs against M. avium complex multiplication within human macrophages. These activities were compar...

show abstract

Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication of Mycobacterium avium complex within human macrophages

Cited by 83 publications

References 22 publications

Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity

Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity

Validated Polarographic Methods for the Determination of Certain Antibacterial Drugs

Activities of WIN-57273, minocycline, clarithromycin, and 14-hydroxy-clarithromycin against Mycobacterium avium complex in human macrophages

Contact Info

Product

Resources

About