Davey,, Peter;PechÈre,, Jean-Claude;Speller,, David
doi: 10.1093/jac/22.Supplement_B.iiipmid: N/A
Article PDF first page preview Close This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
doi: 10.1093/jac/22.Supplement_B.1pmid: 3053564
Abstract 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. This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
Brisson-Noël,, Anne;Trieu-Cuot,, Patrick;Courvalin,, Patrice
doi: 10.1093/jac/22.Supplement_B.13pmid: 3053566
Abstract Macrolide antibiotics constitute a group of 12 to 16-membered lactone rings substituted with one or more sugar residues, some of which may be amino sugars. They inhibit bacterial protein synthesis both in vivo and in vitro with varying potencies. Macrolides are generally bacteriostatic, although some of these drugs may be bactericidal at very high concentrations. The mechanism of action of macrolides has been a matter of controversy for some time. Spiramycin, a 16-membered macrolide, inhibits translocation by binding to bacterial 50S ribosomal subunits with an apparent 1 : 1 stoichiometry. This antibiotic is a potent inhibitor of the binding to the ribosome of both donor and acceptor substrates. Spiramycin induces rapid breakdown of polyribosomes, an effect which has formerly been interpreted as occurring by normal ribosomal run-off followed by an antibiotic-induced block at or shortly after initiation of a new peptide. However, there is now convincing evidence that spiramycin, and probably all macrolides, act primarily by stimulating the dissociation of peptidyl-tRNA from ribosomes during translocation. Although the ribosomes of both Gram-positive and Gram-negative organisms are susceptible to macrolides, these antibiotics are mainly used against Gram-positive bacteria since they are unable to enter the porins of Gram-negative bacteria. Resistance to macrolides in clinical isolates is most frequently due to post-transcriptional methylation of an adenine residue of 23S ribosomal RNA, which leads to co-resistance to macrolides, lincosamides and streptogramins type B (the so-called MLSB phenotype). Other mechanisms of resistance involving cell impermeability or drug inactivation have been detected in Staphylococcus spp. and Escherichia coli. These strains are resistant to 14-membered macrolides (erythromycin and oleandomycin) but remain susceptible to spiramycin. This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
Desnottes, J., F.;Diallo,, N.;Moret,, G.
doi: 10.1093/jac/22.Supplement_B.25pmid: 3182444
Abstract Three strains of Staphylococcus aureus, serotype 18, Cowan I and serotype 66438, and different species of streptococci (Streptococcus pyogenes, Str. mutans, Str. sanguis and Str. faecalis) were tested for their adherence to buccal cells (as measured by interference contrast microscopy) and phagocytosis by rat polymorphonuclear leucocytes (PMNs) (as measured by fluorescence microscopy with a vital fluorochrome, acridine orange). Pretreatment of cocci with serial two-fold dilutions of spiramycin (from 1/2 to 1/1024 the MIC), increased the diameter of bacterial cells and decreased the adherence of staphylococci and streptococci to buccal cells. Exposure of streptococci to 1 /4 the MIC of spiramycin led to an increase of the phagocytic capacity of PMNs. Pretreatment of PMNs with a therapeutic concentration (2 mg/1) also stimulated the phagocytosis of streptococci. Action of spiramycin on the phagocytosis of staphylococci varied according to the strain tested. Although in-vitro results cannot be directly compared with in-vivo data, it is of interest that spiramycin decreases adherence of different Gram-positive cocci and enhances phagocytic capacity of PMNs. This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
Webster,, Carol;Ghazanfar,, Katayoun;Slack,, Richard
doi: 10.1093/jac/22.Supplement_B.33pmid: 3182445
Abstract 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 i MIC produced antibacterial effects. Post-antibiotic effects were more marked with spiramycin. After 3 h exposure to 4 × 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. This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
Buu-Hoï, A., Y.;Goldstein, F., W.;Acar, J., F.
doi: 10.1093/jac/22.Supplement_B.41pmid: 3182446
Abstract During a 17 year period (1970–1986), 2753 clinical isolates of Streptococcus pneumoniae isolated in two hospitals were serotyped and tested for antibiotic susceptibility. In the last ten years the number of multiply resistant strains has increased to 60% of the resistant isolates. Resistance to tetracycline was already present in 14% of the isolates in 1970, and was the most frequent resistance encountered during this study (30% of the strains). Resistance to chloramphenicol was first detected in 1972, but this resistance has remained infrequent (3%). Resistance to penicillin is extremely rare and since 1978, only six strains with relative penicillin resistance (MIC 0·1–1·0 mg/1) have been isolated. Resistance to macrolides, lincosamides and streptogramin B (MLSB resistant phenotype) was first detected in 1976. From 1983 to 1986, 131 isolates were MLSB resistant strains. These strains belonged to 20 different serotypes but 75% of the MLSB resistant pneumococci belonged to serotypes 6, 23, 19 and 14 which were among the most frequently isolated serotypes. In contrast serotypes 3 and 9 were epidemic but not resistant during the same period. Resistance markers in S. pneumoniae are often related to particular serotypes. The large monthly fluctuation in the isolation of resistant strains might explain the variable clinical results of empirical treatment of respiratory infections with macrolides. This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
Riou, J., Y.;Guibourdenche,, M.
doi: 10.1093/jac/22.Supplement_B.53pmid: 3141349
Abstract This in-vitro study of susceptibility to spiramycin of 103 strains of Branhamella catarrhalis isolated between 1982 and 1987 was performed by evaluation of their MICs. More than 97% of strains remained susceptible with MIC less than or equal to 8 mg/1 (two strains). One strain presented a MIC of 16 mg/1. There were no significant differences of susceptibility to spiramycin between penicillinase-producing and non-producing strains. This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
doi: 10.1093/jac/22.Supplement_B.57pmid: 3263355
Abstract Following determination of MICs and MBCs of spiramycin and trimethoprim by the broth microdilution method for 16 typable (including 13 type b) and 15 nontypable H. influenzae isolates, bactericidal synergy was tested by the chequerboard method and the time-kill curve methods. Nineteen (13 typable and six nontypable) of 31 strains demonstrated synergy by the chequerboard method. Ten strains showed indifference, and two manifested antagonism. In contrast, 12/13 strains tested by the time-kill method showed synergy and 1/13 demonstrated indifference. Of note was the finding that seven isolates that showed indifference by chequerboard method (three typable, four nontypable) manifested synergism by the kill-curve method. Of the two nontypable strains showing antagonism by chequerboard, one manifested synergy and the other indifference by the time-kill method. Our studies show that in-vitro synergy between spiramycin and trimethoprim against H. influenzae strains is frequently demonstrable. In-vivo studies may be helpful in confirming these in-vitro observations. This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
Nowicki,, M.;Paucod, J., C.;Bornstein,, N.;Isoard,, P.;Fleurette,, J.
doi: 10.1093/jac/22.Supplement_B.63pmid: 3182447
Abstract The effect of preventive and curative spiramycin therapy was studied in guinea pigs infected by aerosol with the experimental model previously tested. The infectious aerosol was obtained from a virulent strain of Legionella pneumophila (Philadelphia ATCC 33 152). Male guinea pigs (Dunkin-Hartley) weighing 250–300 g were exposed for 30 min to an aerosol of 1 or 10 LD50 (103 or 104 viable inhaled organisms). Spiramycin was administered intraperitoneally (150 mg/kg/day) 18 h after infection for five days for curative therapy; for preventive therapy it was administered on the day before and on the day of aerosol administration (10 LD50). The animals were observed during seven days for weight and temperature and 28 days for survival; bacterial (lungs, spleen) and serological tests were performed. Spiramycin levels (lungs, serum) were evaluated during treatment by a microbiological method. The survival rate in the treated guinea pigs after inhalation of 1 LD50 was 100%. For the 10 LD50 aerosol, curative and preventive therapy gave a survival rate of 87·5%; these results are significant when compared with results of non-treated animals, P < 0·05. Spiramycin merits further study in experimental and human legionellosis. This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
Doumon,, Eric;Rajagopalan,, Premavathy
doi: 10.1093/jac/22.Supplement_B.69pmid: 3182448
Abstract Spiramycin was compared with erythromycin in a guinea pig model of severe Legionella pneumophila serogroup 1 infection. Male guinea pigs weighing 264–321 g were infected by the intraperitioneal route with l·2 × 107 virulent L. pneumophila serogroup 1 . Forty eight h after infection, animals that had lost ⩾ 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. This content is only available as a PDF. © 1988 The British Society for Antimicrobial Chemotherapy
Showing 1 to 10 of 32 Articles