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PubMed2003

Therapeutic effect of spiramycin in brucellosis.

OBJECTIVE: This study was undertaken to investigate the usefulness of spiramycin in treatment for brucellosis in an animal model. METHODS: Eighty-four Sprague-Dawley rats were infected by intraperitoneal injection of Brucella melitensis suspension. Seven days after inoculation, four rats were selected randomly, killed and spleen cultures and Brucella standard tube agglutination test were carried out. All four rats were found to be infected. Eighty adult rats were randomly divided into four groups of 20 rats each. Tap water was given to the first group. Rifampicin 50 mg/kg per day and doxycycline 40 mg/kg per day were given to the second group, spiramycin 50 mg/kg per day orally was given to the third group, and a combination of spiramycin and rifampicin at the same dose and period was given to the fourth group. Duration of therapy regimens in all groups was 21 days. The spleens of all 80 rats were removed aseptically, homogenized, and placed onto Brucella agar plates to determine if viable bacteria were present. RESULTS: Bacterial growth occurred in all of the rats' spleens in the first group and in two rats' spleens in the spiramycin group. Mean colony forming unit (c.f.u.) values were at the highest in the first group. The effectivities of spiramycin and rifampicin-spiramycin were similar to rifampicin-doxycycline. There were no differences in the treatment results between the three groups that received combined rifampicin-doxycycline, rifampicin-spiramycin and only spiramycin (P>0.05). CONCLUSIONS: The results show that spiramycin cures experimental rat brucellosis and may be an effective alternative in the therapy of human brucellosis.

Animals↗
PubMed1994

Pharmacokinetics of spiramycin in the rhesus monkey: transplacental passage and distribution in tissue in the fetus.

Transplacental transfer of spiramycin was investigated in a rhesus monkey model to study whether the antibiotic reaches therapeutic levels in the fetus. Spiramycin concentrations were measured by bioassay and high-performance liquid chromatography. Pharmacokinetic parameters were determined for bioactive spiramycin as measured by the bioassay. Pharmacokinetic pilot studies showed that spiramycin distribution follows a two-compartment model in rhesus monkeys. Following a single intravenous dose of 50 or 250 mg, dose-dependent kinetics were observed. At a dose of 50 mg, 10% of the dose was excreted unchanged in the urine. At the higher dose of 250 mg, an oliguric effect was observed. Spiramycin concentrations in fetal serum were measured over time while the maternal concentration was maintained at a constant level. During a 5-h experiment, a maximum fetal-maternal serum ratio of 0.27 was found. In three fetuses, concentrations in serum and tissue were measured following intravenous administration of 50 mg of spiramycin twice daily to the mother for at least 7 days. The fetal-maternal serum ratios were found to be 0.4 to 0.58 after intravenous administration of the final dose of 50 mg to the mother. It appeared that spiramycin accumulated in the soft tissues, especially in the liver and spleen, of both the mother and the fetus. The concentration in placental tissue appeared to be 10 to 20 times that of the concentration in fetal serum. The concentration of spiramycin in amniotic fluid was about five times higher than the concentration in fetal serum. Another important observation was that absolutely no spiramycin was found in the brain.

Animals↗
PubMed1991

Respiratory tract distribution and bioavailability of spiramycin in calves.

Pharmacokinetic determinants of spiramycin and its distribution into the respiratory tract were studied in 2 groups of calves, 4 to 10 weeks old. Group-A calves (n = 4) were used to determine pharmacokinetic variables of spiramycin after IV (15 and 30 mg/kg of body weight) and oral administrations of the drug (30 mg/kg) and to measure distribution of spiramycin into nasal and bronchial secretions. Group-B calves (n = 4) were used to determine distribution of spiramycin into lung tissue and bronchial mucosa. Spiramycin disposition was best described by use of an open 3-compartment model. Mean (+/- SD) elimination half-life was 28.7 +/- 12.3 hours, and steady-state volume of distribution was 23.5 +/- 6.0 L/kg. Bio-availability after oral administration was 4 +/- 3%. High and persistent concentrations of spiramycin were achieved in the respiratory tract tissues and fluids. Tissue-to-plasma concentration ratio was 58 for lung tissue and 18 for bronchial mucosa at 3 hours after spiramycin administration and 137 and 49, respectively at 24 hours. Secretion-to-plasma concentration ratio was 4 for nasal secretions and 7 for bronchial secretions, and remained almost constant with time. Thus, spiramycin penetrates well into the respiratory tract, although the value in bronchial secretions is lower than that in lung tissues and bronchial mucosa. Calculations indicate that a loading dose of 45 mg/kg, administered IV, followed by a maintenance dose of 20 mg/kg, IV, once daily is required to maintain active concentrations of spiramycin against bovine pathogens in bronchial secretions.

Animals↗
PubMed1998

[Toxoplasmosis retinochorioiditis, a therapy comparison between spiramycin and pyrimethamine/sulfadiazine].

BACKGROUND: The treatment of toxoplasma retinochoroiditis with spiramycin is an alternative to sulfadiazine and pyrimethamine. The treatment with sulfadiazine is associated with multiple side effects. Sulfadiazine is contraindicated during pregnancy and breastfeeding period. Spiramycin has less side effects and is recommended during pregnancy and breastfeeding period. The efficacy of spiramycin in treatment of toxoplasma retinochoroiditis is still a matter of controversy. PATIENTS AND METHODS: In a retrospective study, side effects and outcome of therapy in 44 patients with toxoplasma retinochoroiditis treated with sulfadiazine and pyrimethamine (n = 30) or spiramycin (n = 14) were compared. We assessed duration of therapy and healing, ophthalmoscopic findings and observed side effects. RESULTS: The mean healing time in the group of spiramycin was 63.83 days in comparison to 88 days for the group of patients treated with sulfadiazine/pyrimethamine. The frequency of side effects was lower in the group treated with spiramycin. CONCLUSION: In comparison to a combined application of sulfadiazine and pyrimethamine the treatment with spiramycin alone requires a shorter duration of therapy and healing period. Additionally, side effects and contraindications appear to be less frequent. In view of these findings, spiramycin therapy must be considered as a promising approach in the treatment of toxoplasma retinochoroiditis.

Adult↗
PubMed1991

Coloning and expression of spiramycin polyketide synthase genes and resistance genes from S. spiramyceticus U-1941.

The plasmid containing the spiramycin polyketide synthase genes, pCN3H8, was obtained from the genomic library of spiramycin producing strain, S. spiramyceticus U-1941, using homologous DNA to actI and actIII genes as hybridization probes. Restriction analysis of the plasmid pCN3H8 showed that the molecular weight was 44kb. The regions homologous to the actI & actIII genes were localized by Southern hybridization, and corresponding DNA fragments were subcloned onto E. coli-Streptomyces shuttle vector pWHM3. A recombinant plasmid pCG4 was obtained. Transformation of the pCN3H8 DNA into the polyketide synthase deficient mutant of midecamycin producing strain, S. mycarofaciens subsp. No. 68, resulted in the production of midecamycin A by UV analysis. Transformation of the pCN3H8 DNA into the polyketide synthase deficient mutant of actinorhodin producing strain, S. coelicolor TK17, resulted in the production of an antibacterial compound which was neither similar to actinorhodin in color nor to spiramycin by paper chromatographic analysis. Transformant of S. lividans with pCN3H8 DNA produced an antibacterial compound as well. Resistance to spiramycin was expressed in transformants of spiramycin sensitive strain, S. griseofuscus, with pCN3H8 DNA. A plasmid pSG3 DNA with molecular weight of 7.0kb, isolated from the transformant, might be a result of in vivo deletion of pCN3H8 in S. griseofuscus. Retransformation of pSG3 DNA into S. griseofuscus confirmed that the gene of resistance to spiramycin was on the plasmid pSG3 DNA. Transformation of spiramycin producing strain, S. ambofaciens, with pCG4 or pSG3 DNA increased spiramycin production in fermentation broth.

Cloning, Molecular↗
PubMed1988

Early studies on in-vitro and experimental activity of spiramycin: a review.

This review of spiramycin activity in vitro is based mainly on early studies. The MICs of spiramycin for common pathogenic bacteria such as staphylococci, streptococci and pneumococci are higher than those of erythromycin. Conversely, in experimental models, the activity of spiramycin is equal to or greater than that of erythromycin. In addition, the activity of spiramycin on Neisseria, Legionella, Mycoplasma, Chlamydia, and Toxoplasma spp. completes its antimicrobial spectrum and shows that spiramycin covers the majority of agents responsible for respiratory tract infections. The 'spiramycin paradox'-the discrepancy between the relatively modest activity of spiramycin in vitro and its excellent activity in vivo will be explained by other papers. Its high tissue and intracellular concentrations, and the slow recovery of bacteria submitted to spiramycin are of great importance to account for its activity in vivo.

Bacteria↗
PubMed1982

Genetic and biochemical features of spiramycin biosynthesis in Streptomyces ambofaciens--curing, protoplast regeneration and plasmid transfer.

Spiramycin-producing Streptomyces ambofaciens KA-1028 harboring the pSA1 plasmid gave rise to spiramycin non-producing variants at high frequencies by various curing treatments. However, a number of the spiramycin non-producing progeny obtained by treatment with acridine dyes, still harbored plasmid DNAs which could not be differentiated from plasmid pSA1 by contour length, cleavage patterns and heteroduplex analysis. By treatment with mitomycin C, plasmid pSA1 was cured at high efficiency and spiramycin non-producing strains were obtained. Strain U-1717R obtained by regeneration of protoplasts of plasmid-cured strain U-1717 regained spiramycin production on growth on solid medium only. Furthermore, transconjugants obtained by mating between strain KA-1028 and U-1717R-24 (streptomycin-resistant) regained spiramycin production in both liquid and solid media. We conclude that the genes for the biosynthesis of spiramycin are encoded in a replicon other than plasmid pSA1 but that this plasmid plays a role in the regulation of spiramycin production.

Conjugation, Genetic↗
PubMed1993

Interaction between the antibiotic spiramycin and a ribosomal complex active in peptide bond formation.

The inhibition of peptide bond formation by spiramycin was studied in an in vitro system derived from Escherichia coli. Peptide bonds are formed between puromycin (S) and Ac-Phe-tRNA, which is a component of complex C, i.e., of the [Ac-Phe-tRNA-70S ribosome-poly(U)] complex, according to the puromycin reaction: C+S (Ks)<==>CS (k3)==>C'+P [Synetos, D., & Coutsogeorgopoulos, C. (1987) Biochim. Biophys. Acta 923, 275-285]. It is shown that spiramycin (A) reacts with complex C and forms the spiramycin complex C*A, which is inactive toward puromycin. C*A is the tightest complex formed between complex C and any of a number of antibiotics, such as chloramphenicol, blasticidin S, lincomycin, or sparsomycin. C*A remains stable following gel chromatography on Sephadex G-200 and sucrose gradient ultracentrifugation. Detailed kinetic study suggests that C*A is formed in a variation of a two-step mechanism in which the initial encounter complex CA is kinetically insignificant and C*A is the product of a conformational change of complex CA according to the equation, C+A (kassoc)<==>(kdissoc) C*A. The rate constants of this reaction (spiramycin reaction) are kassoc = 3.0 x 10(4) M-1 s-1 and kdissoc = 5.0 x 10(-5) s-1. Such values allow the classification of spiramycin as a slow-binding, slowly reversible inhibitor; they also lead to the calculation of an apparent overall dissociation constant equal to 1.8 nM for the C*A complex. Furthermore, they render spiramycin a useful tool in the study of antibiotic action on protein synthesis in vitro. Thus, the spiramycin reaction, in conjunction with the puromycin reaction, is applied (i) to detect a strong preincubation effect exerted by chloramphenicol and lincomycin (this effect constitutes further evidence that these two antibiotics combine with complex C as slow-binding inhibitors) and (ii) to determine the rate constant for the regeneration (k7 = 2.0 x 10(-3) s-1) of complex C from the sparsomycin complex C*I [Theocharis, D. A., & Coutsogeorgopoulos, C. (1992) Biochemistry 31, 5861-5868] according to the equation, C+I (Ki)<==>CI (k6)<==>(k7) C*I. The determination of k7 enables us to calculate the apparent association rate constant of sparsomycin, (k7/Ki') = 1.0 x 10(5) M-1 s-1, where Ki' = Ki(k7/k6 + k7). It is also shown that Ac-Phe-tRNA bound to the sparsomycin complex C*I is protected against attack by hydroxylamine.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗
PubMed1998

Bioavailability of spiramycin and lincomycin after oral administration to fed and fasted pigs.

The disposition of spiramycin and lincomycin was measured after intravenous (i.v.) and oral (p.o.) administration to pigs. Twelve healthy pigs (six for each compound) weighing 16-43 kg received a dose of 10 mg/kg intravenously, and 55 mg/kg (spiramycin) or 33 mg/kg (lincomycin) orally in both a fasted and a fed condition in a three-way cross-over design. Spiramycin was detectable in plasma up to 30 h after intravenous and oral administration to both fasted and fed pigs, whereas lincomycin was detected for only 12 h after intravenous administration and up to 15 h after oral administration. The volume of distribution was 5.6 +/- 1.5 and 1.1 +/- 0.2 L/kg body weight for spiramycin and lincomycin, respectively. For both compounds the bioavailability was strongly dependent on the presence of food in the gastrointestinal tract. For spiramycin the bioavailability was determined to be 60% and 24% in fasted and fed pigs, respectively, whereas the corresponding figures for lincomycin were 73% and 41%. The maximum plasma concentration of spiramycin (Cmax) was estimated to be 5 microg/mL in fasted pigs and 1 microg/mL only in fed pigs. It is concluded that an oral dose of 55 mg/kg body weight is not enough to give a therapeutically effective plasma concentration of spiramycin against species of Mycoplasma, Streptococcus, Staphylococcus and Pasteurella multocida. The maximum plasma concentration of lincomycin was estimated to be 8 microg/mL in fasted pigs and 5 microg/mL in fed pigs, but as the minimum inhibitory concentration for lincomycin against Actinobacillus pleuropneumoniae and P. multocida is higher than 32 microg/mL a therapeutically effective plasma concentration could not be obtained following oral administration of the drug. For Mycoplasma the MIC90 is below 1 microg/mL and a therapeutically effective plasma concentration of lincomycin was thus obtained after oral administration to both fed and fasted pigs.

Administration, Oral↗
PubMed1992

Comparative efficacy of spiramycin and erythromycin in acute exudative tonsillitis in adults: a randomized controlled trial.

A randomized control trial was designed to compare the efficacies of spiramycin given one gram twice daily and erythromycin given 500 mg thrice or four times daily in the treatment of acute exudative tonsillitis in adults whose ages were over 13 years old from January 1989 to January 1991 at a community clinic. A total of 120 cases were enrolled in the study. Fifty-three patients received spiramycin while 67 received erythromycin. Group A beta-hemolytic streptococci (GABHS), S. aureus, and positive titer of Mycoplasma pneumoniae were detected in 19, 47 and 8 per cent in spiramycin group and 21, 36 and 11 per cent in erythromycin group respectively. GABHS were totally eradicated on day 3 of treatment in both groups through eradication of S. aureus was slightly slower initially in the spiramycin group. Marked improvement was similarly achieved in both groups after 3 days of therapy. Dyspepsia was felt in 34.4 and 8.2 per cent of erythromycin and spiramycin groups respectively but was tolerable by most patients. We concluded that spiramycin given twice daily was as effectively as conventional erythromycin but spiramycin is more convenient to administer and causes much less gastro-intestinal side-effect.

Acute Disease↗
PubMed1987

Comparative efficacy of clindamycin, erythromycin and spiramycin against Staphylococcus aureus in the rat croton oil pouch model.

Spiramycin, a macrolide antibiotic, has inferior in-vitro activity to erythromycin, but superior tissue penetration. Recent publications have suggested that the in-vivo activity of spiramycin should be re-assessed. The efficacy of clindamycin, erythromycin and spiramycin was compared against Staphylococcus aureus infections in the rat croton oil pouch model. The concentration of spiramycin in the pouch fluid was lower than the concentration of clindamycin or erythromycin after single or multiple intraperitoneal injections. In contrast, the concentration of spiramycin in the pouch wall (73.3 +/- 14.5 micrograms/g) was markedly higher than that of erythromycin (less than 7.5 micrograms/g). Multiple doses of spiramycin had no significant effect upon bacterial growth in the pouch, whereas clindamycin and erythromycin had a significant bactericidal effect. The results suggest that spiramycin is bound to tissues, diffuses poorly into tissue fluid and may therefore be ineffective against infections in large collections of tissue fluid.

Animals↗
PubMed1988

A comparison of the pharmacokinetics and tissue penetration of spiramycin and erythromycin.

The pharmacokinetics of two orally administered macrolides, spiramycin and erythromycin, were compared in six healthy male volunteers in a single dose cross-over study. Penetration of these antimicrobial agents into inflammatory fluid was studied. Spiramycin was administered in a 2 g dose and erythromycin in a 500 mg dose. Spiramycin (Tmax = 3.3 h) and erythromycin (Tmax = 1.2 h) were well absorbed reaching mean plasma Cmax of 3.1 mg/l and 2.1 mg/l, respectively. The relative bioavailability of erythromycin compared to spiramycin appeared to be three- to four-fold greater. The mean plasma elimination half-life was 3.8 h for spiramycin and 1.6 h for erythromycin. The percentage penetration of the antibiotics into inflammatory fluid was good, being 66% for spiramycin and 54% for erythromycin. Both antimicrobial agents attained inflammatory fluid Cmax of 0.7 mg/l by 4-4.8 h. Spiramycin persisted in the inflammatory fluid with a mean elimination half-life of 7.7 h compared to 2.2 h for erythromycin. Twenty-four hour urinary recovery of the administered dose of each antimicrobial agent was less than 5%.

Adult↗
PubMed1988

Prophylaxis of congenital toxoplasmosis. Effects of spiramycin on placental infection.

The results of parasitological investigation of the placenta for toxoplasma in 223 cases with documented congenital toxoplasmosis were analysed according to whether the mother had been treated, or not, with spiramycin during pregnancy. The investigation was negative in 10-11% of the cases when the mother had not been treated or had been inadequately treated; in 25% of the cases with a treatment of 3 g spiramycin day; and in 50% with spiramycin plus the combination of pyrimethamine with sulphonamide. This series is compared with a previous group of 321 women whose placental investigation was negative in 50% of untreated cases and 81% of treated women. The treatment categories are not directly comparable, because it is not possible to have a randomly assigned 'no treatment' group, for ethical reasons. Correlation between spiramycin treatment and negative results of mouse inoculation of placental material suggests that spiramycin might decrease the risk of materno-fetal transmission of toxoplasma by reducing the severity and duration of toxoplasmic placentitis. Current use of spiramycin in infected pregnant women is recommended because of its activity and lack of side effects. The dosage must not be lower than 3 g/day. Additional pyrimethamine plus sulphonamide should be restricted to selected cases with fetal abnormality diagnosed during pregnancy. Some data on pharmacology of spiramycin in mothers, placentas and fetuses are reviewed. They suggest that monitoring of maternal serum antibody titres for a dosage more adapted to individual cases may be desirable.

Female↗
PubMed1988

Sub-inhibitory and post-antibiotic effects of spiramycin and erythromycin on Staphylococcus aureus.

The antibacterial responses of clinical isolates of Staphylococcus aureus to spiramycin and erythromycin were compared. Conventional MICs showed erythromycin-sensitive strains to be 16-32 times less sensitive to spiramycin. MBCs were only four to eight times higher for spiramycin. Erythromycin resistant S. aureus were more frequently encountered. Concentrations of both macrolides at 1/4 MIC produced antibacterial effects. Post-antibiotic effects were more marked with spiramycin. After 3 h exposure to 4 x MIC of antibiotic the delay in regrowth of S. aureus was 5 h for erythromycin and 9 h for spiramycin. In a continuous cultivation model, spiramycin produced an inhibitory effect on S. aureus for 12 h whereas the effect of erythromycin was only apparent for 6 h. In conclusion, spiramycin is more active against staphylococci in vitro than would be expected by its modest MICs.

Drug Resistance, Microbial↗
PubMed1979

Clinical evaluation of spiramycin and erythromycin in control of periodontal disease.

Two studies are reported. Each was double-blind in which Spiramycin was compared to Erythromycin and a placebo, to determine the value of Spiramycin as a therapeutic agent in the control of periodontal disease. In Study 1, 48 adults with varying degrees of periodontal disease were randomly assigned to treatment and control groups. Assessments of gingival index, plaque height, pocket depth, crevicular fluid volume and wet plaque weight were made. During this 4-week clinical trial, the patients maintained their usual oral hygiene. The medication was administered systemically for 5 days, starting at the conclusion of week 2. Spiramycin significantly reduced the scores for the five parameters recorded. When comparison were made, the greatest recorded effect with Spiramycin treatment was found in patients with advanced periodontal disease. The indication of this trend favouring Spiramycin led to an extension of this clinical trial involving only patients with advanced periodontal lesions. This second study comprised 54 adults. The same parameters were measured over the same time period as in Study 1. Spiramycin again was responsible for the greatest reduction in the recorded scores. For example, average pocket depth was decreased by approximately 30%, whereas Erythromycin produced a reduction of 15%. It would appear that Spiramycin is of definite benefit in the management of periodontal disease, especially in the more advanced cases.

Administration, Oral↗
PubMed1993

Efficacy of azithromycin compared with spiramycin in the treatment of odontogenic infections.

Sixty patients with acute odontogenic infections were randomly allocated to oral treatment with azithromycin 500 mg/day once-daily for three days (n = 30) or spiramycin 3,000,000 units three-times daily for seven days (n = 30). Baseline and post-treatment oral specimens were collected from patients to test for pathogenic bacteria. Aerobic bacteria were tested using the Kirby-Bauer disc diffusion method, and anaerobic bacteria with a broth microdilution method, for their susceptibility to azithromycin and spiramycin. A greater incidence of resistance was found in the spiramycin group than in the azithromycin group. The bacteriological assessment showed that the normal balance of microflora was re-established in 67% of patients treated with azithromycin vs 53% in the group treated with spiramycin. Clinical cure was higher in the azithromycin treatment group (97%) compared with the spiramycin group (73%). These results indicate that three-day azithromycin, possibly because of its unusual pharmacokinetics, is more effective than seven-day spiramycin in the treatment of odontogenic infections.

Azithromycin↗
PubMed1998

Congenital toxoplasmosis: efficacy of maternal treatment with spiramycin alone.

PROBLEM: The evidence supporting an additional benefit of a combined regimen of pyrimethamine-sulfonamides compared with spiramycin alone in the secondary prevention of congenital toxoplasmosis was critically evaluated. METHOD OF STUDY: We reviewed the series of cases published in the English literature on antiparasitic treatment of acute toxoplasmosis infection in pregnancy, using spiramycin until fetal infection is documented, then using cycles of spiramycin alternated with combined pyrimethamine-sulfonamide therapy. We then compared the occurrence of overt disease among infected offspring (both severe, represented by ophthalmologic or cerebral abnormalities, and mild occurrences, represented by asymptomatic intracranial calcifications and retinal scars without visual impairment) between the published case series and our consecutive series of cases treated during a 10-year period (January 1986-December 1995) with spiramycin alone. RESULTS: The prevalence of fetal infection in our series was 7.8% (12/154), similar to that reported after alternated regimens (7.0%). The rate of overt disease among infected fetuses is not different after treatment with alternated regimens than after continuous antibiotic spiramycin therapy [23% (19/82) vs. 10% (1/10); relative risk, 2.3; 95% confidence interval, 0.4, 47.0]. The pharmacokinetics of the drugs used may account for this finding. CONCLUSION: The treatment of acute toxoplasmosis in pregnancy with an alternated antibiotic regimen of pyrimethamine-sulfonamide is not more efficacious at preventing overt neonatal disease than treatment with continuous spiramycin alone.

Anti-Infective Agents↗
PubMed1994

Effectiveness of spiramycin for treatment of congenital Toxoplasma gondii infection in rhesus monkeys.

The effectiveness of spiramycin for the treatment of rhesus monkey fetuses congenitally infected with Toxoplasma gondii was studied. Eight monkeys were infected at day 90 of pregnancy. This is comparable to the second trimester of organogenetic development in humans. Transmission of infection was found prenatally in five of the eight monkeys by detection of the parasite in the amniotic fluid. Treatment with spiramycin (20 mg/kg/day in two intermittent doses given intravenously) was started as soon as fetal infection was proven and was continued until birth. Nine to 14 days after initiation of treatment, the parasite was still detectable in amniotic fluid samples from four of these five cases. However, the parasite was detected only by PCR and not by mouse inoculation. T. gondii was also detected only by PCR in the placenta of one monkey that delivered prematurely. This monkey received spiramycin treatment for only 2 weeks. In the four monkeys that received treatment for about 7 weeks, the parasite was not present at birth in the placenta nor in amniotic fluid or neonatal organs. Spiramycin accumulates mainly in maternal tissues. Although concentrations in neonatal tissue were found to be 5 to 28 times higher than the corresponding concentrations in neonatal serum, the concentrations in neonatal tissue were still 11 to 16 times lower than those found in the mothers. However, no spiramycin was found in the fetal brains. Early treatment with spiramycin may prevent transmission of infection to the fetus but most probably cannot interrupt an existing brain infection, which is the most severe outcome of congenital toxoplasmosis in humans.

Amniotic Fluid↗