The prevention of congenital toxoplasmosis using a combination of Spiramycin and Cotrimoxazole: The long-time experience of a tertiary referral centre.

BACKGROUND: Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans-placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection. OBJECTIVES: We report our long-standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin-Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection. METHODS: We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin-Cotrimoxazole. RESULTS: Of 1364 women referred to our centre, postnatal follow-up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin-Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin-Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin-Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin-Cotrimoxazole therapy was significantly lower than the expected rate reported in literature. CONCLUSIONS: A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in-utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity.

Spiramycin-loaded maltodextrin nanoparticles as a promising treatment of toxoplasmosis on murine model.

Despite being the initial choice for treating toxoplasmosis, sulfadiazine and pyrimethamine have limited effectiveness in eliminating the infection and were linked to a variety of adverse effects. Therefore, the search for new effective therapeutic strategies against toxoplasmosis is still required. The current work is the first research to assess the efficacy of spiramycin-loaded maltodextrin nanoparticles (SPM-loaded MNPs) as a novel alternative drug therapy against toxoplasmosis in a murine model. Fifty laboratory-bred Swiss albino mice were divided into five groups: normal control group (GI, n = 10), positive control group (GII, n = 10), orally treated with spiramycin (SPM) alone (GIII, n = 10), intranasal treated with SPM-loaded MNPs (GIV, n = 10), and orally treated with SPM-loaded MNPs (GV, n = 10). Cysts of Toxoplasma gondii ME-49 strain were used to infect the mice. Tested drugs were administered 2 months after the infection. Drug efficacy was assessed by counting brain cysts, histopathological examination, and measures of serum CD19 by flow cytometer. The orally treated group with SPM-loaded MNPs (GV) showed a marked reduction of brain cyst count (88.7%), histopathological improvement changes, and an increasing mean level of CD19 (80.2%) with significant differences. SPM-loaded MNPs showed potent therapeutic effects against chronic toxoplasmosis. Further research should be conducted to assess it in the treatment of human toxoplasmosis, especially during pregnancy.

Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: A multicenter double-blind randomized controlled trial.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8+ T cells than the placebo group at 3 (2.300,P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8+ T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).

A multimodality therapeutic application on Toxoplasma gondii encephalitis utilizing Spiramycin and 'de novo' Ferula asafetida in immunodeficient mice.

This study investigated a 'de Novo' medicinal herb, Ferula asafetida (FA), against toxoplasma encephalitis either alone or combined with spiramycin (SP). Female Swiss-Webster mice (n = 72) were divided into three batches. Batch-I received no DMS to serve as an immunocompetent control, batch-II was immune-suppressed with the DMS (0.25 mg/g/day) for 14 days pre-infection, whilst batch-III was immune-suppressed with the DMS on the same day of infection. All experimental mice were inoculated with Toxoplasma gondii ME49 cysts (n = 75). Each batch was split into four subgroups: Mono-SP, mono-FA, combined drug (SP + FA), or neither. Therapies were administered on day zero of infection in batches (I and II) and 35 days post-infection in batch (III). Treatments lasted for 14 days, and mice were sacrificed 60 days post-infection. Histopathological changes, cysts load, and CD4 and CD8 T-cells were counted in brain tissues. The cyst-load count in mice receiving SP + FA was significantly (p < .0001) the least compared to the mono treatments in all protocols. Interestingly, the combined therapy demolished the T-cell subsets to zero in immunocompetent and immunocompromised infected mice. In conclusion, F. asafetida might be a powerfully natural, safe vehicle of SP in the digestive system and/or across the brain-blood barrier to control toxoplasmosis even through immunodeficient conditions.

Novel experimental design paradigm for development of eco-friendly gradient chromatographic method for simultaneous determination of metronidazole and spiramycin.

This work describes the innovative experimental design-assisted development of a green gradient chromatographic method for concomitant analysis of metronidazole (MTR) and spiramycin (SPR). Two different designs including fractional factorial and Box-Behnken designs were implemented for screening and optimization steps, respectively. The optimum chromatographic conditions involved a mobile phase consisting of ethanol and 20 mM sodium dihydrogen phosphate solution (pH adjusted to 2.5) in the ratio 2:98 (v/v) for 2 min then the ratio changed to 30:70 (v/v). The flow rate was 1.3 mL/minute. Separation and analysis were performed on X-bridge C18 (150 mm × 4.6 mm × 3.5 µm) column with diode array detector set at 230 nm. Column oven temperature was 40°C. A linear response was acquired over the range of 5-125 µg/mL for both drugs. Detection and quantitation limits were 0.86 and 2.62 µg/mL for MTR and 0.92 and 2.83 µg/mL for SPR, respectively. The method was implemented for determination of both drugs in three tablet formulations. The method was proved to be green as evaluated by three assessment tools. The application of experimental designs assists in development of a robust green chromatographic method in gradient elution mode for determination of both drugs within reasonable time.

Novel insights on the therapeutic effect of levamisole on the chronic toxoplasmosis in mice model.

Latent toxoplasmosis mostly reactivates which could result in acute encephalitis. Chronic toxoplasmosis treatments are severely constrained by Toxoplasma cyst resistance. Novel therapeutic approaches are therefore becoming more essential. In this study, the effects of levamisole (LEVA) and spiramycin on the early and late stages of experimental toxoplasmosis are investigated. MATERIALS AND METHODS: Seventy-five Me49 Toxoplasma gondii infected Swiss albino mice were divided into five groups; (GI): noninfected control group; (GII): infected untreated control group; (GIII): infected- LEVA treated group; (GIV): infected and received combination of spiramycin and LEVA and (GV): infected-spiramycin treated group. The impact was assessed through brain cyst count by Quantitative Real-Time Polymerase Chain Reaction (PCR), interferon gamma (IFN-γ) assay, histopathological study, and total blood counts. RESULTS: The progression of chronic toxoplasmosis could only be partially controlled by using either levamisole or spiramycin as a separate drug. The combined spiramycin and levamisole treatment significantly decreased the burden of Toxoplasma brain cyst, increased IFN-γ level, total blood parameters and improved the histopathological features especially at the late stage of infection. IN CONCLUSION: Levamisole effectively modulated Toxoplasma-induced immune responses, resulting in chronic toxoplasmosis remission. Further clinical trials will be needed to study the effect of these combination in HIV/AIDS (human immunodeficiency virus) patients with toxoplasmosis.

16-membered ring macrolides and erythromycin induce ermB expression by different mechanisms.

BACKGROUND: Ribosome stalling on ermBL at the tenth codon (Asp) and mRNA stabilization are believed to be mechanisms by which erythromycin (Ery) induces ermB expression. Expression of ermB is also induced by 16-membered ring macrolides (tylosin, josamycin and spiramycin), but the mechanism underlying this induction is unknown. METHODS: We introduced premature termination codons, alanine-scanning mutagenesis and amino acid mutations in ermBL and ermBL2. RESULTS: In this paper, we demonstrated that 16-membered ring macrolides can induce ermB expression but not ermC expression. The truncated mutants of the ermB-coding sequence indicate that the regulatory regions of ermB whose expression is induced by Ery and 16-membered ring macrolides are different. We proved that translation of the N-terminal region of ermBL is key for the induction of ermB expression by Ery, spiramycin (Spi) and tylosin (Tyl). We also demonstrated that ermBL2 is critical for the induction of ermB expression by erythromycin but not by 16-membered ring macrolides. CONCLUSIONS: The translation of ermBL and the RNA sequence of the C-terminus of ermBL are critical for the induction of ermB expression by Spi and Tyl.

Anti-Inflammatory Effects of Spiramycin in LPS-Activated RAW 264.7 Macrophages.

Drug repurposing is a simple concept with a long history, and is a paradigm shift that can significantly reduce the costs and accelerate the process of bringing a new small-molecule drug into clinical practice. We attempted to uncover a new application of spiramycin, an old medication that was classically prescribed for toxoplasmosis and various other soft-tissue infections; specifically, we initiated a study on the anti-inflammatory capacity of spiramycin. For this purpose, we used murine macrophage RAW 264.7 as a model for this experiment and investigated the anti-inflammatory effects of spiramycin by inhibiting the production of pro-inflammatory mediators and cytokines. In the present study, we demonstrated that spiramycin significantly decreased nitric oxide (NO), interleukin (IL)-1ß, and IL-6 levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Spiramycin also inhibited the expression of NO synthase (iNOS), potentially explaining the spiramycin-induced decrease in NO production. In addition, spiramycin inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs); extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase (JNK) as well as the inactivation and subsequent nuclear translocation of nuclear factor κB (NF-κB). This indicated that spiramycin attenuates macrophages' secretion of IL-6, IL-1ß, and NO, inducing iNOS expression via the inhibition of the NF-κB and MAPK signaling pathways. Finally, we tested the potential application of spiramycin as a topical material by human skin primary irritation tests. It was performed on the normal skin (upper back) of 31 volunteers to determine whether 100 µM and µM of spiramycin had irritation or sensitization potential. In these assays, spiramycin did not induce any adverse reactions. In conclusion, our results demonstrate that spiramycin can effectively attenuate the activation of macrophages, suggesting that spiramycin could be a potential candidate for drug repositioning as a topical anti-inflammatory agent.

Effects of three antibiotics on growth and antioxidant response of Chlorella pyrenoidosa and Anabaena cylindrica.

Antibiotics are essential for treatments of bacterial infection and play important roles in the fields of aquaculture and animal husbandry. Antibiotics are accumulated in water and soil due to the excessive consumption and incomplete treatment of antibiotic wastewater. The accumulation of antibiotics in ecological systems leads to global environmental risks. The toxic effects of spiramycin (SPI), tigecycline (TGC), and amoxicillin (AMX) on Chlorella pyrenoidesa and Anabaena cylindrica were evaluated based on growth inhibition experiments, and determinations of ROS production and antioxidant enzyme activities (catalase, superoxide dismutase, and malondialdehyde). Half maximal effective concentrations (EC50) of TGC, SPI, and AMX for A. cylindrica were 62.52 µg/L, 38.40 µg/L, and 7.66 mg/L, respectively. Those were 6.20 mg/L, 4.58 mg/L, and > 2 g/L for C. pyrenoidesa, respectively. It was shown that A. cylindrica was much more sensitive to these antibiotics than C. pyrenoidesa. In addition, EC50 values of SPI and TGC were lower than that of AMX. It was indicated that SPI and TGC had higher toxic than AMX to C. pyrenoidesa and A. cylindrica. The current study is helpful to evaluating possible ecological risks of TGC, SPI, and AMX by green microalgae and cyanobacteria.

Conversion of biochar to sulfonated solid acid catalysts for spiramycin hydrolysis: Insights into the sulfonation process.

Biochar has been recognized as a sustainable platform for developing functional materials including catalysts. This work demonstrated a method of converting biochar to sulfonated solid-acid catalysts, and the effectiveness of the catalysts for spiramycin hydrolysis was examined. Two biochar samples (H and X) were sulfonated with three reagents (concentrated H2SO4, ClSO3H and p-toluenesulfonic acid (TsOH)) under hydrothermal, simple heating, ambient temperature, and CHCl3-assisted treatments. The effect of elemental compositions and structural characteristics of the feeding materials (H and X) on the acidic properties of the sulfonated biochars were investigated. The results showed that the sulfonation ability of the three reagents was in the order of ClSO3H > H2SO4 > TsOH, while hydrothermal treatment provided the highest total acidity, and largest amount of acidic groups (e.g., SO3H, COOH and Ar-OH). Biochar X with higher O/C and N contents, and less graphitic features showed superior acidic properties than biochar H under all the employed treatments. The hydrolytic efficiencies of the sulfonated biochars under 200 W of microwave irradiation increased with increasing total acidity, and the amount of SO3H and COOH groups. After sulfonation, the O/C of biochars increased, while H/C decreased, and the aromatic and graphitic features did not change. The electromagnetic energy absorbed by the sulfonated biochars did not notably contribute to spiramycin hydrolysis. Thus, this work demonstrated an effective and promising method for maneuvering biochar-based functional solid-acid catalysts for antibiotic remediation in contaminated water.

Comparison of antimicrobial prescribing for dental and oral infections in England and Scotland with Norway and Sweden and their relative contribution to national consumption 2010-2016.

BACKGROUND: Prescribing in dental practice has a relatively small but important contribution to the quantity of antibiotics prescribed in primary care. This study aimed to analyse antibiotic prescribing in dentistry over time (2010-2016) in 4 different Northern European countries and their relative contribution to national outpatients consumption. METHODS: This retrospective study evaluated the frequency and number of national antibiotic prescriptions written by dentists in England, Scotland, Norway and Sweden. The consumption of such antibiotics was measured using WHO defined daily doses (DDDs), DDDs per 100,000 inhabitants per day (DIDs100,000). RESULTS: A total of more than 27 million prescriptions (27,026,599) archived between 2010 and 2016 from the four countries were analysed. The national contribution of Norwegian dentists to the total primary care prescription during this period was 8%. The corresponding figures for Sweden, Scotland and England were 7, 6, and 8%. Dental contribution to National antibiotic use in all four countries has decreased over the study time period for commonly prescribed antibiotics in dentistry, i.e., the beta-lactams (Phenoxymethyl penicillin/Amoxicillin) and metronidazole. There were less numbers of prescriptions by dentists in Norway and Sweden compared to England and Scotland. Marked differences in some classes of antibiotics were noted with Phenoxymethyl penicillin dominating in Sweden/Norway compared to Amoxicillin and Metronidazole in England/Scotland. In England and Scotland, dentists were the largest prescribers of metronidazole in primary care. Clindamycin prescriptions was higher in Norway and Sweden. CONCLUSION: Noticeable differences exist in prescribing patterns for the management of oral infections. High levels of metronidazole use in England and Scotland also require further analysis. All countries over the study period showed a decrease in total numbers of antibiotics prescribed.

Engineering of leucine-responsive regulatory protein improves spiramycin and bitespiramycin biosynthesis.

BACKGROUND: Bitespiramycin (BT) is produced by recombinant spiramycin (SP) producing strain Streptomyces spiramyceticus harboring a heterologous 4″-O-isovaleryltransferase gene (ist). Exogenous L-Leucine (L-Leu) could improve the production of BT. The orf2 gene found from the genomic sequence of S. spiramyceticus encodes a leucine-responsive regulatory protein (Lrp) family regulator named as SSP_Lrp. The functions of SSP_Lrp and L-Leu involved in the biosynthesis of spiramycin (SP) and BT were investigated in S. spiramyceticus. RESULTS: SSP_Lrp was a global regulator directly affecting the expression of three positive regulatory genes, bsm23, bsm42 and acyB2, in SP or BT biosynthesis. Inactivation of SSP_Lrp gene in S. spiramyceticus 1941 caused minor increase of SP production. However, SP production of the ΔSSP_Lrp-SP strain containing an SSP_Lrp deficient of putative L-Leu binding domain was higher than that of S. spiramyceticus 1941 (476.2 ± 3.1 µg/L versus 313.3 ± 25.2 µg/L, respectively), especially SP III increased remarkably. The yield of BT in ΔSSP_Lrp-BT strain was more than twice than that in 1941-BT. The fact that intracellular concentrations of branched-chain amino acids (BCAAs) decreased markedly in the ΔSSP_Lrp-SP demonstrated increasing catabolism of BCAAs provided more precursors for SP biosynthesis. Comparative analysis of transcriptome profiles of the ΔSSP_Lrp-SP and S. spiramyceticus 1941 found 12 genes with obvious differences in expression, including 6 up-regulated genes and 6 down-regulated genes. The up-regulated genes are related to PKS gene for SP biosynthesis, isoprenoid biosynthesis, a Sigma24 family factor, the metabolism of aspartic acid, pyruvate and acyl-CoA; and the down-regulated genes are associated with ribosomal proteins, an AcrR family regulator, and biosynthesis of terpenoid, glutamate and glutamine. CONCLUSION: SSP_Lrp in S. spiramyceticus was a negative regulator involved in the SP and BT biosynthesis. The deletion of SSP_Lrp putative L-Leu binding domain was advantageous for production of BT and SP, especially their III components.

Effectively remediating spiramycin from production wastewater through hydrolyzing its functional groups using solid superacid TiO2/SO4.

Breaking down the structural bonds and eliminating the functional groups are more efficient than destroying the whole molecule in antibiotic production wastewater (APW) pretreatment before further biotreatment. Two sulfated titania (TiO2/SO4) solid superacids, SSA1 and SSA2 were synthesized, characterized and used for hydrolytic pretreatment of spiramycin in APW. Spiramycin removal followed an order of SSA2>SSA1>TiO2≈pH = 3>control. The hydrolytic efficiencies increased at elevated temperature from 25 °C to 65 °C. The hydrolytic kinetics followed a first-order model and SSA2 performed the fastest. The performances were positively correlated with both the total acidity determined by n-butylamine titration and the strength of acid sites measured by NH3-temperature-programmed desorption (TPD). The residual solution for SSA2 presented the least antibacterial potency and anaerobic inhibition among all treatments. The hydrolyzed product was identified as the m/z 699.4321 fragment using UPLC-Q/TOF-MS, which was formed after losing a functional mycarose moiety from the parent molecular. The solid superacids were effective in selectively eliminating 433 mg/L of spiramycin and the antibacterial potencies of the spiramycin production wastewater, which contained very high concentrations of COD (33,000 mg/L). This hydrolytic method avoids using and handling hazardous and corrosive mineral acids on site. It is attractive as a selective catalytic pretreatment method to cleave antibiotics' functional groups and to reduce its inhibitory effects before sequential biotreatments.

Successful treatment of acute experimental toxoplasmosis by spiramycin-loaded chitosan nanoparticles.

Spiramycin-metronidazole and spiramycin-loaded chitosan (CS) nanoparticles (NPs) were tested in comparison with the current spiramycin treatment of T.gondii concerning tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain and were divided into experimental and control groups. The experimental groups orally received CS NPs, spiramycin, spiramycin-metronidazole, spiramycin-loaded CS NPs 400 mg/kg and spiramycin-loaded CS NPs 100 mg/kg. Drug efficacy was assessed by mice survival time, mortality rate, parasite load in different organs and morphological study of the tachyzoites movement by light microscope and the ultra-structure by SEM. The results revealed that the maximum survival time of more than 200 days with no mortality on the sacrifice day (8th) was observed in mice receiving spiramycin-loaded NPs. Spiramycin-loaded NPs showed the highest significant percent reduction of tachyzoites (about 90% reduction) in liver, spleen and brain as compared to the other used drugs denoting successful bypass of BBB. Light microscopy of the treated peritoneal tachyzoites showed sluggish tachyzoites movement while the NPs caused loss of their movement. SEM of the treated tachyzoites were more mutilated and some of them appeared rupturing in those receiving CS NPs and spiramycin-loaded NPs. In conclusion, spiramycin-loaded NPs showed the highest efficiency in the treatment of acute toxoplasmosis. The non-toxic nature and the anti-parasitic effect of both CS and spiramycin make the use of spiramycin-loaded CS NPs a potential material for treatment of human toxoplasmosis.

Sub-10-nm multicolored gold nanoparticles for colorimetric determination of antibiotics via formation of interlocking rings.

A general approach is presented for synthesis of multicolored gold nanoparticles (GNPs) by Au(I)-mediated generation of interlocking rings in proteins and antibiotics. The Au(I) ions are shuttled from proteins to antibiotics, and this causes the formation of interlocking rings. The multicolored GNPs of different sizes were synthesized in the rings by using the rapid nucleation method. To take the unique colors of GNPs, a functional array was designed for the colorimetric determination and discrimination of antibiotics, specifically of amoxicillin, chlortetracycline, erythromycin, spiramycin, neomycin, thiamphenicol, gentamycin and lincomycin. The method is based on the "three color" (RGB) principle. The color response patterns are characteristic for each antibiotic and can be quantitatively differentiated by statistical techniques. The limits of detection (LOD, at S/N = 3) for spiramycin (Sp) have been calculated to be 0.18 µM and 0.10 µM in water and milk, respectively. The good linear range (from 0.3 to 3.5 µM) has been used for the quantitative assay of Sp in a certified reference material. Graphical abstractSchematic presentation of gold nanoparticles (GNPs) synthesis via formation of interlocking rings in protein and antibiotics. The Au(I) ions mediate protein and antibiotics to be interlocking rings, which are quickly fixed via microwave reaction. The GNPs are synthesized and assembled in the rings.

Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: a multicenter, randomized trial.

BACKGROUND: The efficacy of prophylaxis to prevent prenatal toxoplasmosis transmission is controversial, without any previous randomized clinical trial. In France, spiramycin is usually prescribed for maternal seroconversions. A more potent pyrimethamine + sulfadiazine regimen is used to treat congenital toxoplasmosis and is offered in some countries as prophylaxis. OBJECTIVE: We sought to compare the efficacy and tolerance of pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission. STUDY DESIGN: This was a randomized, open-label trial in 36 French centers, comparing pyrimethamine (50 mg qd) + sulfadiazine (1 g tid) with folinic acid vs spiramycin (1 g tid) following toxoplasmosis seroconversion. RESULTS: In all, 143 women were randomized from November 2010 through January 2014. An amniocentesis was later performed in 131 cases, with a positive Toxoplasma gondii polymerase chain reaction in 7/67 (10.4%) in the pyrimethamine + sulfadiazine group vs 13/64 (20.3%) in the spiramycin group. Cerebral ultrasound anomalies appeared in 0/73 fetuses in the pyrimethamine + sulfadiazine group, vs 6/70 in the spiramycin group (P = .01). Two of these pregnancies were terminated. Transmission rates, excluding 18 children with undefined status, were 12/65 in the pyrimethamine + sulfadiazine group (18.5%), vs 18/60 in the spiramycin group (30%, P = .147), equivalent to an odds ratio of 0.53 (95% confidence interval, 0.23-1.22) and which after adjustment tended to be stronger (P = .03 for interaction) when treatment started within 3 weeks of seroconversion (95% confidence interval, 0.00-1.63). Two women had severe rashes, both with pyrimethamine + sulfadiazine. CONCLUSION: There was a trend toward lower transmission with pyrimethamine + sulfadiazine, but it did not reach statistical significance, possibly for lack of statistical power because enrollment was discontinued. There were also no fetal cerebral toxoplasmosis lesions in the pyrimethamine + sulfadiazine group. These promising results encourage further research on chemoprophylaxis to prevent congenital toxoplasmosis.

Antibiotic effects on seed germination and root development of tomato (Solanum lycopersicum L.).

Antibiotics are emerging pollutants released into the environment through wastewater and manure or effluents from livestock plants. Compared to the wide literature on the effects of antibiotics on the development of drug-resistant bacteria and on the adverse effects on animals and human beings, the effects on plants are less investigated. Here we evaluated the effects of four antibiotics (cloramphenicol: CAP, spiramycin: SPR, spectinomycin: SPT, vancomycin: VAN) belonging to different chemical groups, on seed germination and root development of tomato (Solanum lycopersicum L. cv. San Marzano). Specifically, seed germination and root elongation kinetics, as well as the number of mithotic figures in root apical meristem, were studied in relation to different concentrations of each antibiotic (0, 0.1, 1, 10, 100, 1000mgL-1) for 10 and 7 days, respectively. Results showed that seed germination was not affected, but root development (root elongation kinetics and cell division) was impaired at concentrations from 10mgL-1 (SPT) and 100mgL-1 (CAP) to 1000mgL-1 (SPR and VAN).

Anaerobic biodegradation of spiramycin I and characterization of its new metabolites.

Activated sludge was used to treat the wastewater containing spiramycin I. Three new metabolites were isolated and identified, which produced by oxidation of C6-aldehyde, hydrolysis of C5-mycaminose-mycarose and macrolactone ring-open reaction of spiramycin I in anaerobic digestion. And their antimicrobial activities were inactivated. Our results indicated that anaerobic biodegradation metabolites of spiramycin I could not induce bacterial resistance in environment.

Influence of Al3+ on the titer of spiramycin and effective components in fermentor.

Spiramycin is a multicomponent antibiotic, and different components have different antibacterial activities. In Streptomyces spiramyceticus 16-10-2, spiramycin II and spiramycin III (SPMII and SPMIII) are the main components, while spiramycin I (SPMI) needs to be controlled below 12%. Based on this, the influences of Al3+ on total spiramycin titer and components were investigated in this work. Those experiments were mainly performed in 15 L fermentor and Al3+ made a great improvement in spiramycin titer. The optimal adding concentration and adding time of Al3+ were 0.32 g/L at 12 hr. Under this condition, spiramycin titer was increased by 19.51% compared with the control. Moreover, the percentage of SPMII and SPMIII was increased by 7.14%. At the same time, the time of mycelia autolysis was lengthened. In addition, the specific activities of acetyl-CoA synthetase, acetate kinase, acetylphosphotransferase, and acylating enzyme were much higher than those of control. The content of acetic acid and succinic acid was beyond 3 and 4.5 times than that of control, respectively.

Visible light driven mineralization of spiramycin over photostructured N-doped TiO2 on up conversion phosphors.

A novel visible light-active photocatalyst formulation (NdT/OP) was obtained by supporting N-doped TiO2 (NdT) particles on up-conversion luminescent organic phosphors (OP). The photocatalytic activity of such catalysts was evaluated for the mineralization process of spiramycin in aqueous solution. The effect of NdT loading in the range 15-60wt.% on bulk and surface characteristics of NdT/OP catalysts was investigated by several chemico-physical characterization techniques. The photocatalytic performance of NdT/OP catalysts in the removal of spyramicin from aqueous solution was assessed through photocatalytic tests under visible light irradiation. Total organic carbon (TOC) of aqueous solution, and CO and CO2 gas concentrations evolved during the photodegradation were analyzed. A dramatic enhancement of photocatalytic activity of the photostructured visible active NdT/OP catalysts, compared to NdT catalyst, was observed. Only CO2 was detected in gas-phase during visible light irradiation, proving that the photocatalytic process is effective in the mineralization of spiramycin, reaching very high values of TOC removal. The photocatalyst NdT/OP at 30wt.% of NdT loading showed the highest photocatalytic activity (58% of TOC removed after 180min irradiation against only 31% removal after 300min of irradiation of NdT). We attribute this enhanced activity to the high effectiveness in the utilization of visible light through improved light harvesting and exploiting. OP particles act as "photoactive support", able to be excited by the external visible light irradiation, and reissue luminescence of wavelength suitable to promote NdT photomineralization activity.