Activity of clarithromycin alone or in combination with other drugs for treatment of murine toxoplasmosis

Araujo, Fausto G.; Prokocimer, Philippe; Lin, TY; Remington, J S

doi:10.1128/aac.36.11.2454

Cited by 45 publications

(19 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(8,10,17,41), and Toxoplasma gondii (3,7,12). In comparison with erythromycin, clarithromycin showed improved pharmacokinetic properties, including the maximum concentration of drug in the serum of patients treated with up to 4 p,g/ml (9,19), and a high intracellular concentration of the drug, with intracellular to extracellular concentration ratios of 30 to 40 (2).…”

Section: Discussionmentioning

confidence: 99%

In vitro susceptibilities of spotted fever group rickettsiae and Coxiella burnetti to clarithromycin

Maurin

Raoult

1993

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The in vitro bacteriostatic activity of clarithromycin, a new macrolide derivative, against Rickettsia rickettsii, Rickettsia conorii, and "Rickettsia israeli" was determined by the plaque assay and the dye uptake assay. Both bacteriostatic and bactericidal activities of clarithromycin against the Nine Mile, Q212, Priscilla, and ME9 strains of Coxiella burnetii were evaluated by using three cell culture systems. Clarithromycin showed improved antibacterial activity compared with that of erythromycin. A bacteriostatic activity was obtained at concentrations below the reported maximum concentration of clarithromycin in human serum (about 4 ,ug/ml) for all tested rickettsiae. MICs ranged from 1 to 2 ,ug/ml for the three Rickettsia species and from 1 to 4 ,ug/ml for the C. burnetii strains. No bactericidal activity against C. burnetii was obtained when clarithromycin was used at 4 ,ug/ml.Rickettsia rickettsii is the etiologic agent of Rocky Mountain spotted fever, Rickettsia conorii is the etiologic agent of Mediterranean spotted fever (MSF), and "Rickettsia israeli" is responsible for a spotted fever without "tache noire" in Israel (20,21). Coxiella burnetii is the etiologic agent of Q fever, a widely distributed zoonosis. C. burnetii infections may present as an acute disease, such as hepatitis, pneumonitis, and self-limited febrile illness, or a chronic disease, mainly endocarditis. Bacteria of the genera Rickettsia and Coxiella are obligate intracellular pathogens, the former being located in the cytoplasm (16,42,45) and the latter being located in the phagolysosomes (1, 22) of infected host cells.Tetracyclines remain the antibiotics of choice for the treatment of rickettsial diseases, with chloramphenicol and the fluoroquinolones used as alternative drugs (27,32,33,37,46). However, severe forms of Rocky Mountain spotted fever and MSF have been described (38, 44), especially when appropriate antibiotic treatment was delayed. Whereas acute C. burnetii infections respond to antibiotic therapy with tetracyclines, chronic C. burnetii infections are hard to cure, and we have previously demonstrated that the antibiotic compounds used against C. burnetii have no in vitro bactericidal activity (25). On the other hand, because of potential adverse effects, tetracyclines and fluoroquinolones are not recommended for use during pregnancy and childhood, and chloramphenicol may be responsible for aplastic anemia.Erythromycin is considered not to be a reliable treatment for diseases caused by R conorii (33). Authors have emphasized the susceptibility heterogeneity among different strains of C. burnetii to macrolides, which may explain why erythromycin may be considered effective or not effective in treating Q fever (31a). More recently, in vitro experiments have shown that the macrolides josamycin and roxithromycin are effective against R. conorii and R. rickettshi (13,35 4 ,ug/ml (9, 19) and that it is highly concentrated within eukaryotic cells (2). MATERIALS AND METHODSAntibiotic preparation. Clarithromycin (Abbott Labora...

show abstract

Section: Discussionmentioning

confidence: 99%

In vitro susceptibilities of spotted fever group rickettsiae and Coxiella burnetti to clarithromycin

Maurin

Raoult

1993

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…The first vaccination dose was given, followed 10 days later by the second dose and the third dose was given 20 days after the second dose. Mice of groups 1 and 2 were challenged four weeks after the last vaccination dose by 2,500 viable tachyzoites of RH strain injected intraperitoneally, the same dose of viable tachyzoites was used for infecting mice of group 3 and 4 (Araujo et al 1992). …”

Section: Experimental Animals Infection and Vaccination Schedulementioning

confidence: 99%

A comparative study between excretory/secretory and autoclaved vaccines against RH strain of Toxoplasma gondii in murine models

et al. 2013

View full text Add to dashboard Cite

Toxoplasma gondii is an obligate intracellular protozoan that has a major importance in public health, in addition to veterinary medicine. Therefore, the development of an effective vaccine for controlling toxoplasmosis is an important goal. Excretory/secretory antigens (ESA), were previously identified as potential vaccine candidates, proved to play important roles in the pathogenesis and immune escape of the parasite. In addition, autoclaved Toxoplasma vaccine (ATV) is a special type of killed vaccine, recently characterized. The aim of the present work was, to compare between excretory/secretory and ATV against RH strain of T. gondii in mice based on; parasitological and histopathological levels. Tachyzoites were harvested from peritoneal exudates of infected mice and were used for challenge infection and vaccine preparation. BCG was used as an adjuvant. Mice were allocated equally into five groups; they were vaccinated intradermally over the sternum. The results of this study showed that the survival time after challenge, extended up to 16 days in ESA vaccinated group and up to 15 days in autoclaved Toxoplasma vaccinated group. ESA vaccinated group exhibited a profound decrease in parasite load following parasite challenge with a higher percentage of reduction in parasite count in all examined organs than the autoclaved Toxoplasma vaccinated group. The histopathological picture of the liver in both immunized groups, revealed marked reduction in the pathological changes observed as compared to controls, especially in ESA vaccinated group. It was concluded that vaccination with ESA showed more promising results versus ATV, as demonstrated by the survival rate of vaccinated mice, tachyzoites count and histopathological examination.

show abstract

“…Previous studies have explored the effects of various combinations including PYR and SDZ against T. gondii. In experimental toxoplasmosis models like mice, the molecules such as trovafloxacin (21), gatifloxacin (22), roxithromycin (23), clarithromycin (24), azithromycin (25), atovaquone (26), and hydroxynaphthoquinones such as PHNQ6 (27), two 3-alkyl-substituted 2-hydroxy-1,4-naphthoquinones NSC52, and NSC55 (28) have been investigated either as monotherapies or in combination with PYR and SDZ. These studies have demonstrated the synergic effects of the combinations, and significant elongations of survival periods have been observed with combination therapies.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Efficacy of Drugs against <i>Toxoplasma gondii</i> Combined with Immunomodulators

Köksal

Yanık²,

Bılgın

et al. 2016

Jpn J Infect Dis

View full text Add to dashboard Cite

SUMMARY:The aim of this study is to evaluate the effects of pyrimethamine (PYR) and sulfadiazine (SDZ) combined with levamisole and echinacea on the survival of mice infected with Toxoplasma gondii. For this, we used 99 specific pathogen-free BALB/c mice. All the mice were infected intraperitoneally with 10 5 T. gondii tachyzoites and were divided into 11 groups, each including 9 mice. Except for the control group, oral treatment was initiated in all groups 24 h post infection and was continued for 10 days. The treatment regimen included dual combinations of PYR (dose, 6.25 and 12.5 mg/kg/day) and SDZ (dose, 100 and 200 mg/kg/day), triple combinations of PYR ＋ SDZ, and levamisole (dose, 2.5 mg/kg/day) or echinacea (dose, 130 and 260 mg/kg/day) and echinacea alone (dose, 130 and 260 mg/kg/day). We observed that an effective dose of the combination of PYR ＋ SDZ and levamisole resulted in a statistically significant increase in the survival rate from 33.3z to 88.9z. Similarly, half the dose of this combination resulted an increase in the survival rate from 0z to 44.4z ( p ＜ 0.05). Survival rate also increased in the groups treated with the combinations including echinacea; however, the difference did not reach statistical significance. The triple combination of PYR-SDZ-levamisole could be an alternative treatment option in case of infections caused by T. gondii.

show abstract

Activity of clarithromycin alone or in combination with other drugs for treatment of murine toxoplasmosis

Cited by 45 publications

References 11 publications

In vitro susceptibilities of spotted fever group rickettsiae and Coxiella burnetti to clarithromycin

In vitro susceptibilities of spotted fever group rickettsiae and Coxiella burnetti to clarithromycin

A comparative study between excretory/secretory and autoclaved vaccines against RH strain of Toxoplasma gondii in murine models

In Vivo Efficacy of Drugs against <i>Toxoplasma gondii</i> Combined with Immunomodulators

Contact Info

Product

Resources

About