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PubMed1988

Comparison of spiramycin and erythromycin in the treatment of experimental guinea pig legionellosis.

Spiramycin was compared with erythromycin in a guinea pig model of severe Legionella pneumophila serogroup 1 infection. Male guinea pigs weighting 264-321 g were infected by the intraperitoneal route with 1.2 x 10(7) virulent L. pneumophila serogroup 1. Forty eight h after infection, animals that had lost greater than or equal to 9% of their body weight were randomly assigned to receive 48, 54 and 72 h after infection intraperitoneal injections of (1) distilled water (n = 20), (2) erythromycin lactobionate, 30 mg/kg per injection, (n = 22) or (3) the injectable form of spiramycin adipate, 30 mg/kg per injection (n = 22). Animals were observed daily for 15 days. All infected animals treated with distilled water died within four days of infection. Of the 22 animals treated with spiramycin, 10 (45.5%) died, and of the 22 animals treated with erythromycin, 11 (50.0%) died of disseminated L. pneumophila infection. In this animal model of very severe L. pneumophila infection, the injectable forms of erythromycin and of spiramycin gave similar results. Spiramycin should therefore be considered for the treatment of Legionnaires' disease in man.

Animals↗
PubMed1979

Bronchial asthma and dermatitis due to spiramycin in a chick breeder.

A case of bronchial asthma and dermatitis due to spiramycin is described in a non-atopic woman who worked as a chick breeder and handling poultry feed containing antibiotic or chemoterapic drugs including spiramycin, chlortetracycline and sulfadimethoxine. Patch tests showed a vigorous delayed reaction to spiramycin. Inhalation challenge test with the chick feed containing spiramycin reproduced symptoms of late asthmatic response (FEV1 fell by 14% and FEF25-75 by 25% within the 4th and 6th hour) with leucocytosis. No significant modification of FEV1 and FEF25-75 was observed within 24 hours after challenge with chick feeds containing other antibiotic or chemotherapeutic agents but not spiramycin. On leaving her job, the patient had no further skin reactions or bronchial asthma episodes. This case suggests that allergic reactions to a chemical product may involve both type III and IV hypersensitivity.

Adult↗
PubMed1979

Bioconversion and biosynthesis of 16-membered macrolide antibiotics. XIII. Regulation of spiramycin I 3-hydroxyl acylase formation by glucose, butyrate, and cerulenin.

The effects of glucose, butyrate, and cerulenin on the formation of spiramycin I 3-hydroxyl acylase were investigated by using the cell-free extract prepared from the spiramycin-producing strain of Streptomyces ambofaciens KA-1028. Glucose induced the formation of the acylase, and this induction was remarkably repressed by butyrate. Cerulenin, on the other hand, not only cancelled the repression by butyrate but also stimulated the formation of the acylase. The unsuccessful trapping of spiramycin I as an intermediate during the bioconversion from neospiramycin I to spiramycin III in the presence of cerulenin was due to the rapid acylation of spiramycin I caused by the acylase induced by cerulenin.

Acyltransferases↗
PubMed1989

Spiramycin vs. placebo for treatment of acute diarrhea caused by Cryptosporidium.

The efficacy of spiramycin was evaluated in a double blind, placebo-controlled study of 44 immunocompetent infants ages 2 to 13 months who had acute diarrhea caused by Cryptosporidium. Twenty-one patients received spiramycin (100 mg/kg/day) for 10 days and 23 received placebo. On admission the patients in both groups were comparable regarding demographic and clinical characteristics. The infants who were treated with spiramycin had a shorter duration of diarrhea (mean, 5.2 vs. 7.3 days; P = 0.002) and a shorter duration of excretion of oocysts in the stools (7.1 vs. 8.5 days; P = 0.032) compared with those treated with placebo. No clinical or parasitologic relapses were seen in patients of both groups. Mild adverse effects to spiramycin were observed in 2 patients (10%). Spiramycin appeared to hasten clinical recovery and decrease the duration of oocyst excretion in immunocompetent children with diarrheal illness caused by Cryptosporidium.

Animals↗
PubMed1992

Effect of sexual steroid hormones on spiramycin disposition in genital tract secretions of the ewe.

The present work investigated the influence of sexual steroid compounds (estradiol 17 beta and fluorogestone) on antibiotic passage across the uterine barrier. Five healthy and mature ewes, with controlled hormonal impregnation, were given a single iv injection of spiramycin, a macrolide antibiotic, at a dose of 64,000 IU/kg. Plasma and uterine secretions were regularly sampled before the injection and for 30 h post-injection. Blood was collected from the jugular vein and uterine secretions were obtained by uterine flushing with a sterile saline solution containing 0.2% inulin. Spiramycin was concentrated in the uterine secretions, whatever the hormonal status; the secretions-to-plasma ratio was 4.68 +/- 1.88 under estrogen priming and 2.68 +/- 0.91 under progestagen priming. The area under the concentration-time curve (AUC) and the mean residence time (MRT) were significantly higher (p less than 0.001) in uterine secretions than in plasma. The AUC in uterine secretions was significantly higher (p less than 0.05) under estrogen priming (439.07 +/- 241.25 IU.h/mL) than under progestagen priming (141.41 +/- 89.37 IU.h/mL). The spiramycin MRTs in uterine secretions were 11.92 +/- 4.08 and 12.06 +/- 3.35 h for both estrogens and progestagen treatment, respectively. These experiments demonstrate that estrogens increase uterine bioavailability, but not the residence time, of spiramycin when administered by a systemic route.

Animals↗
PubMed1998

In vitro interaction between spiramycin and polymorphonuclear neutrophils oxidative metabolism.

PMNs are a major component of body defense against microbial invasion, involving reactive oxygen species in great quantity, which could benefit from antibiotic therapy. Recently, possible antibiotic effects on phagocyte functions (impairment or stimulation of reactive oxygen species production) were studied. In our study, an in vitro evaluation was made on macrolide activity on phagocyte respiratory burst functions, using assay of superoxide anion (O2.-) in response to four stimuli systems: N-formyl Met-Leu-Phe (fMLP), an analogue of bacterial chemotactic factors; 4 beta-phorbol 12-myristate 13-acetate (PMA), a direct activator of protein kinase C (PKC); calcium ionophore (A23187), which acts directly on calcium influx; and a bacterial strain, Staphylococcus aureus. We have shown that spiramycin, at therapeutic plasma concentrations, increased O2.- generation by bacteria and fMLP-stimulated PMNs, with rate of 26% for 1 microgram ml-1 and 34% for 5 micrograms ml-1, respectively. This pro-oxidant effect, however, weaker, was observed when PMNs were stimulated by PMA. A weak anti-oxidant effect was observed with A23187. For higher concentrations, spiramycin decreased strongly O2.- production, with IC50 values of 74 micrograms ml-1, 154 micrograms ml-1, 296 micrograms ml-1 and 400 micrograms ml-1 when PMNs were stimulated with bacteria, A23187, fMLP and PMA, respectively. The effect of spiramycin seemed to result from an intracellular mechanism by intervention of PMN oxidative metabolism (NADPH-oxidase activation), rather than a simple chemical interaction, because no effect has been observed in acellular models. For higher spiramycin concentrations, the decrease of O2.- production observed could not be taken into consideration because this concentration was not used in therapy. The enhanced of O2.- production observed could be used in therapy, so as to increase PMNs bactericidal activity.

Anti-Bacterial Agents↗
PubMed1992

Influence of short-chain fatty acids on the production of spiramycin by Streptomyces ambofaciens.

The addition of short-chain fatty acids stimulates the production of spiramycin by Streptomyces ambofaciens cultivated on dextrins and ammonium chloride. The fatty acids were activated by two enzymatic systems. The first system (acyl-CoA synthetases) was present only during the exponential phase. The second system (acylkinases coupled with acylphosphotransferases) was synthesized during the growth phase and during the stationary phase, in which spiramycin production started. Short-chain fatty acids induced the synthesis of acylkinases and acylphosphotransferases. Added at the beginning of cultures, they increased the specific activity of these enzymes during the exponential growth phase. Added at the early stationary phase, the specific activity of these enzymes and of the spiramycin production increased. Excess ammonium in the culture considerably lowered the specific activity of acylkinases synthesized in the stationary phase, when spiramycin production started. This ammonium effect can be reduced by the addition of short-chain fatty acids.

Acetate Kinase↗
PubMed2004

Improved production of spiramycin by mutant Streptomyces ambofaciens.

Strain improvement and medium optimization to increase the productivity of spiramycin were carried out. Of oil tolerant mutant strains screened, one mutant, Streptomyces ambofaciens XC 2-37, produced 9% more spiramycin than the parent strain S. ambofaciens XC 1-29. The effects of soybean oil and propyl alcohol on spiramycin production with S. ambofaciens XC 2-37 were studied. The potency of S. ambofaciens XC 2-37 was improved by 61.8% with addition of 2% soybean oil in the fermentation medium and 0.4% propyl alcohol at 24 hours after incubation. The suitable time for feeding propyl alcohol is at 24 hours after incubation in flask fermentation and at 20 hours after incubation in fermentor fermentation. The new process with S. ambofaciens XC 2-37 was scaled up for industrial scale production of spiramycin in a 60 m(3) fermentor in Xinchang Pharmaceutical Factory, Zhejiang Medicine Company, Ltd., China, and the potency and productivity of fermentation were improved by 42.9%.

1-Propanol↗
PubMed2005

Effects of glucose limitation on biomass and spiramycin production by Streptomyces ambofaciens.

Spiramycin production by Streptomyces ambofaciens Sp181110 with glucose as the carbon source was studied under a controlled nutritional environment. In a batch culture, the glucose excess after ammonium depletion led to pyruvate and alpha-ketoglutarate accumulation. 85 mg/l of spiramycin were produced in less than 70 h during the stationary and maintenance phase on these acids after glucose exhaustion. Fed-batch strategy was designed to study spiramycin production without by-product formation and glucose accumulation. In these conditions, up to 150 mg/l were produced in less than 80 h during the stationary phase on glucose. The antibiotic titre was found independent of the glucose feeding under carbon limitation and the importance of putative intracellular reserves formed after nutrient exhaustion was suggested. Besides, spiramycin production was not inhibited by the limiting flux of glucose.

Biomass↗
PubMed1991

Distribution of penicillin-G and spiramycin to tissue cages and subcutaneous tissue fluid in calves.

Antibacterial drug concentrations in serum, tissue cage fluid (TCF) and subcutaneous tissue fluid (SF), sampled either by filter paper discs or by microcapillaries, were measured after single intramuscular injections of potassium penicillin-G (KPG), procaine penicillin-G (PPG) and spiramycin adipate in calves. Concentration-time curves had essentially similar profiles in serum and SF, but peak levels were lower and occurred later in SF. From approximately four hours after drug administration, penicillin-G levels in SF were similar to levels in serum after KPG as well as after PPG administration. Elimination half-life (t1/2) of penicillin-G in serum was similar to t1/2 in SF after PPG administration but was longer in SF than in serum after KPG administration. Spiramycin concentrations were higher in SF than in serum and the t1/2 of spiramycin in SF was longer than in serum. For all three drugs, the t1/2 was longer in TCF than in serum and concentration-time curves in TCF were characterised by a slow rise and decline. The two methods of sampling SF, by filter paper discs and by microcapillaries, gave similar but not identical results. Penetration into SF and TCF, measured as the total area under curve ratio, was better for spiramycin than for penicillin-G, but the latter drug had a higher penetration ratio to TCF in the first 12 hours.

Animals↗
PubMed1991

Effect of oral spiramycin on the faecal and oral bacteria in human volunteers.

Six healthy adult volunteers were treated with 1 g of oral spiramycin twice daily for five days, and their oral and faecal microbial flora were studied. Mean saliva and serum concentrations of the antibiotic never exceeded 2.1 +/- 1.1 mg/l. The number of volunteers whose oral cavity was colonized by Enterobacteriaceae, group D streptococci, staphylococci, and fungi remained unchanged following treatment. The mean count of anaerobic faecal bacteria was 10.3 +/- 0.6 log10 cfu/g initially. This did not change significantly during the treatment, nor did the composition of the predominant anaerobic flora. Mean counts of group D streptococci were 1000 times lower than those of anaerobes before treatment, and also remained unchanged during therapy. No overgrowth of fungi, staphylococci, or Pseudomonas aeruginosa was observed. No significant modifications occurred in the mean total count of faecal Enterobacteriaceae (7.9 +/- 0.4 versus 7.4 +/- 1.0 log10 cfu/g of faeces before and during treatment respectively). However, faecal concentrations of highly spiramycin-resistant Enterobacteriaceae (MIC greater than or equal to 512 mg/l) increased from 4.8 +/- 1.2 to 7.0 +/- 1.8 log10 cfu/g during treatment. The MIC50 value of spiramycin for anaerobes, Enterobacteriaceae, and group D streptococci were 0.125, 64, and 0.5 mg/l respectively before treatment, and these increased to 1024, 512 and 1024 mg/l respectively during treatment. This was attributed to the rise in the faecal concentrations of spiramycin, which reached 689 +/- 48 micrograms/g of faeces on the fifth day of treatment. These concentrations decreased rapidly on cessation of treatment.

Administration, Oral↗
PubMed1997

In-vitro activity of spiramycin and metronidazole alone or in combination against clinical isolates from odontogenic abscesses.

One hundred and forty-eight isolates of bacteria from 20 intraoral odontogenic abscesses were tested for their susceptibility to spiramycin and metronidazole alone or in combination. All isolates, except Rothia spp. (one), Enterococcus avium (three), Haemophilus parainfluenzae (one) and Staphylococcus aureus (one) were sensitive to spiramycin and/or metronidazole. Among the anaerobes, spiramycin as well as metronidazole showed good antimicrobial activity against species of Prevotella, Eubacterium, Peptostreptococcus, Bacteroides and Porphyromonas. All the aerobes were resistant to metronidazole. A potential synergic effect was found in 17% of the clinical isolates tested, as the MICs of spiramycin and metronidazole for 25 isolates (21 isolates of Eubacterium, two of lactobacilli, one strain of Peptostreptococcus sp. and one Clostridium clostridiiforme) were significantly reduced by the addition of the other antibiotic.

Anti-Bacterial Agents↗
PubMed1993

Comparison of spiramycin and doxycycline for treatment of Chlamydia trachomatis genital infections.

We performed a single blind controlled multicenter study in which we compared the efficacy and safety of 100 mg of doxycycline versus those of 1 g (3 x 10(6) IU) of spiramycin given orally twice daily for 14 days in the treatment of culture-positive Chlamydia trachomatis genitourinary tract infections. A total of 367 patients were enrolled in the study, and 364 patients were evaluable for safety and 265 patients were evaluable for efficacy. The cure rate between treatment groups was not statistically significant, being 98% (125 of 128 patients) in the spiramycin group and 100% (133 of 133 patients) in the doxycycline group. Female patients who received spiramycin were more likely to report dysethesias that resolved after the completion of therapy. The results of the study show that spiramycin is an effective drug for the treatment of C. trachomatis infection and warrants further assessment over a shorter treatment period (7 days) and during pregnancy.

Adult↗
PubMed1989

Effects of adjunctive treatment of periodontitis with tetracycline and spiramycin.

The present study was undertaken to compare the efficacy of two antibiotics, spiramycin and tetracycline, with a placebo when used adjunctively with scaling and root planing in the treatment of advanced adult chronic periodontitis. This was a double-blind, parallel, randomized trial with one factor (drug) at three levels. Ninety-six patients (mean age 46 +/- 1) were randomly assigned into one of three groups. All groups were scaled and root planed with each respective group receiving either spiramycin, tetracycline, or a placebo for 2 weeks. Two sites with probing depth of at least 7 mm were evaluated and the following clinical parameters were measured at baseline, 2, 8, 12, and 24 weeks: plaque index, bleeding on probing, crevicular fluid, probing depth, and change in the attachment level. The changes in the subgingival bacteria were monitored also using a differential staining technique. Seventy-nine patients completed the study. At the end of 24 weeks, although all three groups had shown clinical improvement when compared to the baseline data, there were no significant intergroup differences in any of the clinical parameters measured. While the proportion of spirochetes were significantly decreased (P less than 0.05) at 2- and 8-week intervals in both tetracycline and spiramycin groups (26% to 0.04% and 28% to 0.04%, respectively), compared to the placebo group (30% to 7%), only in the spiramycin group was the proportion of spirochetes significantly lower than the placebo group at the 24-week interval (3% and 11%, respectively). At week 24, the proportion of spirochetes in the tetracycline group had rebounded to 7%, which was not significantly different from the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

[Clinical efficacy and safety of spiramycin and clarithromycin in the treatment of outpatients with lower respiratory tract infections].

Macrolide antibiotics have a broad spectrum of activities against the common pathogens responsible for lower respiratory tract infections, therefore for over 40 years they have been useful in treatment of these diseases. The aim of this open randomised multicentre trial is to compare the efficacy and safety of spiramycin, one of the first macrolides, to clarithromycin, a new generation macrolide, in their normal condition of use in patient presenting with acute non-complicated lower respiratory tract infections. 55 adult non-hospitalised patients with clinical diagnosis of bronchitis or pneumonia were randomised to receive either spiramycin 3 MIU twice daily or clarithromycin 500 mg twice daily for 7 or 10 days. For clinical evaluable patients, successful outcome was noted for 96.15% (25/26) spiramycin-treated patients and 96.43% (27/28) clarithromycin-treated patients. Clinically significant improvement in signs and symptoms was comparable between treatment groups. 2 patients in the spiramycin group (7.69%) and 3 in clarithromycin group (10.71%) complained of adverse events which severity was mild or moderate and did not require interruption of conducting antibioticotherapy. Efficacy and safety analysis showed that the two macrolides were equally effective and well-tolerated, at the given doses, for the treatment of lower respiratory tract infections and may play important role in out-patient therapy of these diseases.

Adult↗
PubMed1999

Comparison of spiramycin and clarithromycin for community-acquired lower respiratory tract infections.

This open multicentre study compared the efficacy and tolerability of clarithromycin and spiramycin in the treatment of lower respiratory tract infections in Brazil and Colombia. A total of 125 patients with a clinical and radiological diagnosis of pneumonia, acute bronchitis or exacerbation of chronic bronchitis were randomised to receive oral doses of either clarithromycin (500 mg) or spiramycin (3 MIU) every 12 hours for courses of 5-10 days. Patients were assessed before the start of treatment, and at days 3-4 and days 9-17. Twenty-six (26) patients (16 in the spiramycin group and 10 in the clarithromycin group) reported adverse events, seven of whom withdrew from the trial. Statistical analysis detected no significant differences between efficacy (p = 0.768) or tolerability (p = 0.236) for the two treatment groups. Spiramycin therefore has similar efficacy to clarithromycin in the treatment of community-acquired lower respiratory tract infections.

Adolescent↗
PubMed1994

Pharmacokinetics and tissue residues of spiramycin in cattle after intramuscular administration of multiple doses.

Pharmacokinetic variables of spiramycin and its distribution in muscle, liver, kidney, and injection sites were studied in 18 mixed-sex 1-year-old calves to assess drug withdrawal time after 2 IM administrations of 100,000 IU of spiramycin/kg of body weight at 48-hour intervals. Presence of a compound, other than spiramycin I (ie, neospiramycin), was observed in tissues used for withdrawal time determination. High concentrations observed at the injection sites decreased slowly to maximal residue limit with half-life of 109.5 hours for neospiramycin and 77.5 hours for spiramycin. At 14 days, neospiramycin concentrations were higher in kidney than in liver and half-life was different between these 2 tissues. Two methods of withdrawal time determination were used and the part of the samples without residue detected, in the calculation, was discussed. Withdrawal time of 35 days can be proposed on the basis of average daily intake determined for spiramycin, with concentration at injection sites representing 10% of the whole muscle concentration.

Animals↗
PubMed1987

Metronidazole and spiramycin in abscesses caused by Bacteroides spp. and Staphylococcus aureus in mice.

The activity of metronidazole and spiramycin, singly or in combination, was tested in vitro and also in vivo, in the eradication of infection caused by Bacteroides spp. and Staphylococcus aureus, alone or in combination. The MICs of metronidazole for the B. melaninogenicus and B. fragilis strains were significantly reduced by the addition of spiramycin (from 0.25 and 0.5 mg/l, to 0.062 and 0.125 mg/l, respectively). Antimicrobial synergy between metronidazole and spiramycin was noted against Bacteroides spp. in abscesses caused in mice by subcutaneous injection of Bacteroides spp. alone or in combination with S. aureus. Furthermore, an additional reduction in the number of S. aureus was noted in mixed infections with bacteroides that were treated with metronidazole alone. The antimicrobial synergy in vitro and in vivo between metronidazole and spiramycin may have clinical implications that deserve to be further investigated.

Abscess↗