In vitro evaluation of CP-62,993, erythromycin, clindamycin, and tetracycline against Chlamydia trachomatis

Walsh, M.A.; Kappus, Elizabeth W.; Quinn, Thomas C.

doi:10.1128/aac.31.5.811

Cited by 37 publications

(25 citation statements)

References 9 publications

(11 reference statements)

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“…In vitro susceptibility studies have indicated superior or equivalent activity for azithromycin compared with erythromycin, tetracycline, and clindamycin when it is tested against several species of bacteria (12). Our results indicate that azithromycin is highly active in protecting mice against death due to a lethal infection with T. gondii.…”

supporting

confidence: 53%

Azithromycin, a macrolide antibiotic with potent activity against Toxoplasma gondii

Araujo

Guptill

Remington

1988

Antimicrob Agents Chemother

117

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Doses of 200 mg of azithromycin per kg (body weight) administered by the oral route daily for 10 days completely protected mice against death caused by intraperitoneal infection with Toxoplasma gondii. The same treatment regimen also protected 80% of mice infected intracerebrally, which suggests that azithromycin attains active concentrations in the inflamed central nervous system. Toxoplasma gondii has long been recognized as an important opportunistic protozoan for immunocompromised individuals (10). With the increased use of immunosuppressive therapy and the advent of acquired immunodeficiency syndromes, T. gondii has become one of the leading causes of encephalitis in immunosuppressed patients (2). The treatment of choice for toxoplasmosis is the synergistic combination of pyrimethamine and a sulfonamide (5). The optimum duration of treatment has not been determined because of the variable course and severity of the infection. Both drugs are potentially toxic; pyrimethamine is an inhibitor of dihydrofolate reductase, and prolonged therapy may result in depression of the bone marrow, a potentially serious side effect particularly in immunocompromised patients (7, 10). In addition, pyrimethamine is teratogenic, and its use during pregnancy is not recommended. In this case, spiramycin, a macrolide antibiotic that is not readily available to physicians in the United States, is recommended and widely used in Europe, particularly in France (6, 9). Alternative drugs, such as trimethoprim-sulfamethoxazole or clindamycin, have been shown to have activity in vitro and in mouse models, but clinical studies to establish their efficacy have not been conducted. There is thus a critical need for an evaluation of new drugs and drug combinations for the treatment of toxoplasmosis, especially drugs that can be safely used during pregnancy and in immunocompromised patients and drugs that are active in infections of the central nervous system. Azithromycin, a macrolide antibiotic, was provided in powdered form by Pfizer Inc. (Groton, Conn.). The drug was dissolved in a small volume of 95% ethanol, and the desired concentrations for oral administration by gavage to SwissWebster adult female mice (18 to 20 g; Simonsen Laboratories, Gilroy, Calif.) were prepared in polyethylene glycol 200 (J. T. Baker Chemical Co., Phillipsburg, N.J.). Control animals received polyethylene glycol 200 only. Water and pelleted chow were available to the animals at all times.Trophozoites of the RH or C56 strain of T. gondii were obtained from acutely infected mice as previously described (1,8). In experiments in which RH trophozoites were used, mice were inoculated intraperitoneally (i.p.); when C56 trophozoites were used, mice were inoculated intracerebrally as previously described by Hofflin et al. (8). A statistical analysis of the results was performed by the chi-square test (11). * Corresponding author.To determine the activity of azithromycin against T. gondii, mice were infected i.p. with 102 RH trophozoites and 24 h later they were treated wi...

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supporting

confidence: 53%

Azithromycin, a macrolide antibiotic with potent activity against Toxoplasma gondii

Araujo

Guptill

Remington

1988

Antimicrob Agents Chemother

117

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“…For tetracycline, a concentration range above 0.50 g/ml was not included in determining this linear regression since the inhibition plateaued at 0.50 g/ml. Importantly, the plateau of the reduction capability of infected cells at this concentration is consistent with a previously reported observation by IFA that 0.51 g/ml was sufficient to achieve 100% inhibition of C. trachomatis serovar L2 (19). Furthermore, no significant effect on the reduction capability was observed when cells were incubated with antibiotics alone (data not shown).…”

supporting

confidence: 79%

Simple Resazurin-Based Microplate Assay for Measuring Chlamydia Infections

Osaka

Hefty

2013

Antimicrob Agents Chemother

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The conventional method for quantification of Chlamydia infection using fluorescence microscopy typically involves time-and labor-intensive manual enumeration, which is not applicable for a large-scale analysis required for an inhibitory compound screen. In this study, an alamarBlue (resazurin) assay was adopted to measure Chlamydia infection by measuring the redox capability of infected host cells in a 96-well format. The assay provided measurements comparable to those of the conventional microscopy method while drastically reducing the time required for analysis.

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“…Regarding other pathogens of the respiratory tract and auditory canal, azithromycin was 2-to 8-fold more active against H. influenzae, Haemophilus parainfluenzae, B. catarrhalis, and Legionella pneumophila (4,29,65) and more than 10-fold more active against Pasteurella multocida (65) and Mycoplasma pneumoniae and M. hominis (67). It was more potent against N. gonorrhoeae (65) and Ureaplasma urealyticum (67) while comparable to erythromycin against C. trachomatis (78). Activity against Campylobacter species and a variety of anaerobic bacteria varied from slightly higher to slightly lower than that of erythromycin (22,65).…”

mentioning

confidence: 99%

New directions for macrolide antibiotics: structural modifications and in vitro activity

Kirst

Sides

1989

Antimicrob Agents Chemother

152

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In vitro evaluation of CP-62,993, erythromycin, clindamycin, and tetracycline against Chlamydia trachomatis

Cited by 37 publications

References 9 publications

Azithromycin, a macrolide antibiotic with potent activity against Toxoplasma gondii

Azithromycin, a macrolide antibiotic with potent activity against Toxoplasma gondii

Simple Resazurin-Based Microplate Assay for Measuring Chlamydia Infections

New directions for macrolide antibiotics: structural modifications and in vitro activity

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