No abstract

The in vivo effects of antimicrobial agents against Toxoplasma gondii were evaluated in mice that were infected intraperitoneally with 104 tachyzoites of the RH strain by determination of survival rates and study of the kinetics of growth of T. gondi in infected mice. At various intervals after infection, subcultures of serial dilutions of blood, lung, and brain homogenates were performed in fibroblast tissue cultures for determination of parasitic loads. Pyrimethamine (18.5 mg/kg per day), sulfadiazine (375 mg/kg per day), and clindamycin (300 mg/kg per day) were administered for 10 days from day 1 or day 4 after infection. Untreated control mice died within 9 days and showed early and predominant lung involvement. All mice treated with sulfadiazine administered from day 1 survived and were apparently healthy; parasitic loads decreased early after treatment, but a relapse was observed 5 days after the cessation of therapy. When pyrimethamine was administered from day 1, 7 of 11 mice died within 25 days; by determination of parasitic loads, the effect of pyrimethamine was only demonstrable from day 6, and a relapse was constantly observed after the cessation of therapy. When pyrimethamine and sulfadiazine were administered in combination, 100% of mice survived; when therapy was started at day 1, parasites remained undetectable; in mice treated from day 4, parasites were eradicated by day 8 but infection relapsed 8 days after the cessation of therapy. All mice treated with clindamycin from day 1 or day 4 died within 10 days, but parasitemia was always undetectable. These results indicate that study of the kinetics of parasitic loads in blood and organs may provide additional information on the effect of antimicrobial agents against T. gondii in regard to the evolution of the infection and may represent a reliable basis for the determination of therapeutic regimens in humans.In vivo experimental studies of Toxoplasma gondii are usually performed in mice that are either acutely infected by intraperitoneal injection of tachyzoites or chronically infected by peroral ingestion or intraperitoneal injection of cysts. Another alternative, which better fits with the pathophysiology of toxoplasmosis in immunocompromised human patients, is to induce a reactivation in chronically infected mice by depleting the CD4+ lymphocyte subpopulation (19), administering anti-gamma interferon (18), or creating a model of intracerebral infection by local injection of tachyzoites (11,12). Assessment of the efficacy of antimicrobial agents is based on the comparative study of mean survival times of untreated and treated mice, enumeration of brain cysts, and in some cases, histologic examination of organs and subinoculation to mice of dilutions of organ homogenates. The survival rate is an important parameter which can be determined easily but which is poorly informative regarding the mode of drug action. Since additional histological studies and mice subinoculations are time-consuming and may not be applied for extensive studies, we propos...

Two out of 20 children with no known antibiotic exposure, living in a very remote Senegalese village, were found to be fecal carriers of a multiresistant Escherichia coli clone that produced CTX-M-15. This highlights the current massive spread of extended-spectrum β-lactamases, even in isolated communities.