Systematic computer analysis of fundamental and clinical studies on spiramycin pharmacology

Background. Spiramycin is a macrolide antibiotic characterized by minimal resistance to various strains of pathogenic bacteria and a good safety profile. Although the pharmacology of spiramycin has been the subject of many publications, these data are yet to be systematized.
Objective: To systematize all available scientific publications on spiramycin pharmacology.
Material and methods. All currently available publications on basic and clinical studies of spiramycin were analyzed. The query “spiramycin OR rovamycine OR RP 5337” returned 1,755 reports in the PubMed/MEDLINE biomedical database. This sample of publications was then systematically analyzed using the topological and metric approaches to the analysis of heterogeneous feature descriptions that are adopted by the scientific school of Yu.I. Zhuravlev and K.V. Rudakov (Academicians of the RAS). Results. A cluster analysis of the most informative terms describing the pharmacological properties of spiramycin revealed that it is a unique macrolide characterized by targeted tissue accumulation and significantly higher safety than other antibiotics. This safety of spiramycin underlies its successful use to treat toxoplasmosis in pregnant women and prevent maternal-to-fetal transmission of the parasite Toxoplasma gondii. Spiramycin also holds promise for the treatment of other urogenital infections (chlamydia and non-gonococcal urethritis), as well as against oral pathogens that cause caries, gingivitis, and periodontitis. Spiramycin's targeted accumulation in lung tissue allows it to be used against respiratory pathogens, including upper and lower respiratory tract infections. Spiramycin was shown to have anti-inflammatory, anti-tumor, and other additional effects (e.g., anti-obesity).
Conclusion. Spiramycin is characterized by targeted tissue accumulation; it exhibits no significant concomitant toxicity, causes no micronutrient loss (including magnesium, whose deficiency results in QT interval prolongation on the electrocardiogram), and, unlike some other macrolides, has no stimulating effect on resistance development in bacterial pathogens. These properties of the spiramycin molecule indicate promising potential for its use in the inhibition and eradication of bacterial strains resistant to other antibiotics.

1. Kum E., İnce E. Metabolomics approach to explore bioactive natural products derived from plant-root-associated streptomyces. Appl Biochem Biotechnol. 2024; 196 (10): 7293–306. https://doi.org/10.1007/s12010-024-04905-7.

2. Parker C.T., Garrity G.M. Nomenclature Abstract for Streptomyces ambofaciens Pinnert-Sindico 1954 (Approved Lists 1980) emend. Nouioui et al. 2018. https://doi.org/10.1601/nm.6849.

3. Cosar C., Ninet L., Pinnert-Sindico S., Preud'Homme J. Trypanocide action of an antibiotic produced by a streptomyces. C R Hebd Seances Acad Sci. 1952; 234 (14): 1498–9 (in French).

4. Kavi J., Webberley J.M., Andrews J.M., Wise R. A comparison of the pharmacokinetics and tissue penetration of spiramycin and erythromycin. J Antimicrob Chemother. 1988; 22 (Suppl B): 105–10. https://doi.org/10.1093/jac/22.supplement_b.105.

5. Ardila C.M., Bedoya-García J.A. Antimicrobial resistance in patients with odontogenic infections: a systematic scoping review of prospective and experimental studies. J Clin Exp Dent. 2022; 14 (10): e834-45. https://doi.org/10.4317/jced.59830.

6. Torshin I.Yu. On solvability, regularity, and locality of the problem of genome annotation. Pattern Recognit Image Anal. 2010; 20: 386–95. https://doi.org/10.1134/S1054661810030156.

7. Gromova O.A., Torshin I.Yu., Kobalava Zh.D., et al. Deficit of magnesium and states of hypercoagulation: intellectual analysis of data obtained from a sample of patients aged 18–50 years from medical and preventive facilities in Russia. Kardiologiia. 2018; 58 (4): 22–35 (in Russ.). https://doi.org/10.18087/cardio.2018.4.10106.

8. Torshin I.Yu., Gromova O.A., Stakhovskaya L.V., et al. Analysis of 19.9 million publications from the PubMed/MEDLINE database using artificial intelligence methods: approaches to the generalizations of accumulated data and the phenomenon of “fake news”. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020; 13 (2): 146–63 (in Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.021.

9. Torshin I.Yu. On optimization problems arising from the application of topological data analysis to the search for forecasting algorithms with fixed correctors. Informatics and Applications. 2023; 17 (2): 2–10 (in Russ.). https://doi.org/10.14357/19922264230201.

10. Torshin I.Yu. On the formation of sets of precedents based on tables of heterogeneous feature descriptions by methods of topological theory of data analysis. Informatics and Applications. 2023; 17 (3): 2–7 (in Russ.). https://doi.org/10.14357/19922264230301.

11. Frydman A.M., Le Roux Y., Desnottes J.F., et al. Pharmacokinetics of spiramycin in man. J Antimicrob Chemother. 1988; 22 (Suppl B): 93–103. https://doi.org/10.14357/199222642302011093/jac/22.supplement_b.93.

12. Smith C.R. The spiramycin paradox. J Antimicrob Chemother. 1988; 22 (Suppl B): 141–4. https://doi.org/10.1093/jac/22.supplement_b.141.

13. Yakovlev S.V., Suvorova М.Р. The renaissance of spiramycin in clinical practice. Antibiotiki i khimioterapiya / Antibiotics and Chemotherapy. 2023; 68 (7–8): 83–9. (In Russ.) https://doi.org/10.37489/0235-2990-2023-68-7-8-83-89.

14. Franco P.S., Gomes A.O., Barbosa B.F., et al. Azithromycin and spiramycin induce anti-inflammatory response in human trophoblastic (BeWo) cells infected by Toxoplasma gondii but are able to control infection. Placenta. 2011; 32 (11): 838–44. https://doi.org/10.1016/j.placenta.2011.08.012.

15. Grujić J., Djurković-Djaković O., Nikolić A., et al. Effectiveness of spiramycin in murine models of acute and chronic toxoplasmosis. Int J Antimicrob Agents. 2005; 25 (3): 226–30. https://doi.org/10.1016/j.ijantimicag.2004.09.015.

16. Chew W.K., Segarra I., Ambu S., Mak J.W. Significant reduction of brain cysts caused by Toxoplasma gondii after treatment with spiramycin coadministered with metronidazole in a mouse model of chronic toxoplasmosis. Antimicrob Agents Chemother. 2012; 56 (4): 1762–8. https://doi.org/10.1128/AAC.05183-11.

17. El Saftawy E.A., Turkistani S.A., Alghabban H.M., et al. Effects of Lactobacilli acidophilus and/or spiramycin as an adjunct in toxoplasmosis infection challenged with diabetes. Food Waterborne Parasitol. 2023; 32: e00201. https://doi.org/10.1016/j.fawpar.2023.e00201.

18. Berrébi A., Assouline C., Bessières M.H., et al. Long-term outcome of children with congenital toxoplasmosis. Am J Obstet Gynecol. 2010; 203 (6): 552.e1–6. https://doi.org/10.1016/j.ajog.2010.06.002.

19. Cetinkaya Demir B., Yuruk O., Heper Y., Ozkan H. Toxoplasmosis in pregnancy; analysis of maternal seropositivity in a large cohort in Turkey and clinical consequences of neonates. Medicine. 2025; 104 (40): e44881. https://doi.org/10.1097/MD.0000000000044881.

20. De Santis M., Tartaglia S., Apicella M., et al. The prevention of congenital toxoplasmosis using a combination of Spiramycin and Cotrimoxazole: the long-time experience of a tertiary referral centre. Trop Med Int Health. 2024; 29 (8): 697–705. https://doi.org/10.1111/tmi.14021.

21. Ribeiro S.K., Mariano I.M., Cunha A.C.R., et al. Treatment protocols for gestational and congenital toxoplasmosis: a systematic review and meta-analysis. Microorganisms. 2025; 13 (4): 723. https://doi.org/10.3390/microorganisms13040723.

22. Montoya J.G., Laessig K., Fazeli M.S., et al. A fresh look at the role of spiramycin in preventing a neglected disease: meta-analyses of observational studies. Eur J Med Res. 2021; 26 (1): 143. https://doi.org/10.1186/s40001-021-00606-7.

23. Hotop A., Hlobil H., Gross U. Efficacy of rapid treatment initiation following primary Toxoplasma gondii infection during pregnancy. Clin Infect Dis. 2012; 54 (11): 1545–52. https://doi.org/10.1093/cid/cis234.

24. Thiébaut R., Leproust S., Chêne G., Gilbert R. Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients' data. Lancet. 2007; 369 (9556): 115–22. https://doi.org/10.1016/S0140-6736(07)60072-5.

25. Masata J., Rezácová J., Sodja I. Treatment of chlamydial urogenital infections. Ceska Gynekol. 1998; 63 (4): 279–82 (in Czech).

26. Orfila J., Haider F., Thomas D. Activity of spiramycin against chlamydia, in vitro and in vivo. J Antimicrob Chemother. 1988; 22 (Suppl. B): 73–6. https://doi.org/10.1093/jac/22.supplement_b.73.

27. Segev S., Samra Z., Eliav E., et al. The efficacy and safety of spiramycin in the treatment of nongonococcal urethritis in men. J Antimicrob Chemother. 1988; 22 (Suppl. B): 183–7. https://doi.org/10.1093/jac/22.supplement_b.183.

28. Chiappe V., Gómez M., Fernández-Canigia L., Romanelli H. The effect of spiramycin on Porphyromonas gingivalis and other “classic” periopathogens. Acta Odontol Latinoam. 2011; 24 (1): 115–21.

29. Ravishankar P.L., Venugopal K., Nadkerny P. Effect of tetracycline hydrochloride and spiramycin sub gingival irrigation with pulsated jet irrigator in chronic periodontitis patients: a clinical study. J Int Oral Health. 2015; 7 (7): 102–7.

30. Lakhssassi N., Sixou M. Efficacy variation of erythromycin and spiramycin on periopathogens in aggressive periodontitis. An in vitro comparative study. Pathol Biol. 2005; 53 (8–9): 527–35 (in French). https://doi.org/10.1016/j.patbio.2005.06.008.

31. Rams T.E., Dujardin S., Sautter J.D., et al. Spiramycin resistance in human periodontitis microbiota. Anaerobe. 2011; 17 (4): 201–5. https://doi.org/10.1016/j.anaerobe.2011.03.017.

32. Roche Y., Yoshimori R.N. In-vitro activity of spiramycin and metronidazole alone or in combination against clinical isolates from odontogenic abscesses. J Antimicrob Chemother. 1997; 40 (3): 353–7. https://doi.org/10.1093/jac/40.3.353.

33. Bergogne-Bérézin E. Spiramycin concentrations in the human respiratory tract: a review. J Antimicrob Chemother. 1988; 22 (Suppl. B): 117–22. https://doi.org/10.1093/jac/22.supplement_b.117.

34. Kitzis M., Desnottes J.F., Brunel D., et al. Spiramycin concentrations in lung tissue. J Antimicrob Chemother. 1988; 22 (Suppl. B): 123–6. https://doi.org/10.1093/jac/22.supplement_b.123.

35. Sutherland R. Spiramycin: a reappraisal of its antibacterial activity. Br J Pharmacol Chemother. 1962; 19 (1): 99–110. https://doi.org/10.1111/j.1476-5381.1962.tb01430.x.

36. Rondini G., Cocuzza C.E., Cianflone M., et al. Bacteriological and clinical efficacy of various antibiotics used in the treatment of streptococcal pharyngitis in Italy. An epidemiological study. Int J Antimicrob Agents. 2001; 18 (1): 9–17. https://doi.org/10.1016/s0924-8579(01)00342-9.

37. Jeannin L., Vergeret J., Caillaud D., et al. Community-acquired pneumonia in healthy adults: 188 patients treated with spiramycin in private practice. Rev Pneumol Clin. 1992; 48 (6): 263–8 (in French).

38. Mgbor N.C., Umeh R.E. A blind parallel comparative study of the efficacy and safety of rovamycin versus augmentin in the treatment of acute otitis media. West Afr J Med. 2002; 21 (2): 117–20.

39. De Cock L., Poels R. Comparison of spiramycin with erythromycin for lower respiratory tract infections. J Antimicrob Chemother. 1988; 22 (Suppl. B): 159–63. https://doi.org/10.1093/jac/22.supplement_b.159.

40. Gromovа O.A., Torshin I.Yu. Chemoinformatic study of spiramycin in comparison with other antibiotics. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2025; 18 (1): 80–94 (in Russ.).

41. Vazquez D. Binding to ribosomes and inhibitory effect on protein synthesis of the spiramycin antibiotics. Life Sci. 1967; 6 (8): 845–53. https://doi.org/10.1016/0024-3205(67)90287-1.

42. Sáez-Llorens X., Odio C.M., Umaña M.A., Morales M.V. Spiramycin vs. placebo for treatment of acute diarrhea caused by Cryptosporidium. Pediatr Infect Dis J. 1989; 8 (3): 136–40.

43. Mayaud C., Dournon E., Montagne V., et al. Efficacy of intravenous spiramycin in the treatment of severe Legionnaires' disease. J Antimicrob Chemother. 1988; 22 (Suppl. B): 179–82. https://doi.org/10.1093/jac/22.supplement_b.179.

44. Stuart J.G., Ferretti J.J. Genetic analysis of antibiotic resistance in Streptococcus pyogenes. J Bacteriol. 1978; 133 (2): 852–9. https://doi.org/10.1128/jb.133.2.852-859.1978.

45. Chabbert Y.A. Early studies on in-vitro and experimental activity of spiramycin: a review. J Antimicrob Chemother. 1988; 22 (Suppl. B): 1–11. https://doi.org/10.1093/jac/22.supplement_b.1.

46. Brook I. Synergy between spiramycin and metronidazole in the treatment of polymicrobial infections. J Antimicrob Chemother. 1988; 22 (Suppl. B): 77–85. https://doi.org/10.1093/jac/22.supplement_b.77.

47. Avci M.E., Arslan F., Çiftçi Ş., et al. Role of spiramycin in prevention of fetal toxoplasmosis. J Matern Fetal Neonatal Med. 2016; 29 (13): 2073–6. https://doi.org/10.3109/14767058.2015.1074998.

48. Descotes J., Vial T., Delattre D., Evreux J.C. Spiramycin: safety in man. J Antimicrob Chemother. 1988; 22 (Suppl. B): 207–10. https://doi.org/10.1093/jac/22.supplement_b.207.

49. Torshin I.Yu., Kalacheva A.G., Gromova O.A., Rogozin M.A. Evaluation of ATX rubricator drugs by chemoreactome screening method for prevention of magnesium and pyridoxine deficiencies. Pharmacokinetics and Pharmacodynamics. 2025; 3: 21–9 (in Russ.). https://doi.org/10.37489/2587-7836-2025-3-21-29.

50. Gromova O.A., Torshin I.Yu., Limanova O.A., et al. Antibiotic therapy provokes development of magnesium deficiency. What is to be done? Farmateka. 2016; 14: 6–13.

51. Clinical guidelines “Ventricular arrhythmias in adults” (approved by the Ministry of Health of Russia), 2016. Available at: https://library.mededtech.ru/rest/documents/cr_244 (in Russ.) (accessed 20.11.2025).

52. Kang J.K., Kang H.K., Hyun C.G. Anti-inflammatory effects of spiramycin in LPS-activated RAW 264.7 macrophages. Molecules. 2022; 27 (10): 3202. https://doi.org/10.3390/molecules27103202.

53. Neuweiler W., Ritter P. Rovamycin therapy of puerperal mastitis. Geburtshilfe Frauenheilkd. 1957; 17 (5): 405–13.

54. Matsuda M., Goto A., Saito H., et al. Suppressive effect of spiramycin on cell division. Jpn J Antibiot. 2003; 56 (Suppl. A): 121–3 (in Japanese).

55. Wang Z., Cheng J., Wen H., et al. Synthesis, anticancer and antibacterial evaluation of novel spiramycin-acylated derivatives. RSC Adv. 2024; 14 (52): 38898–907. https://doi.org/10.1039/d4ra03126a.

56. Yang R., Otkur W., Feng T., et al. Uncovering anticancer mechanisms of spiramycin derivatives using transcriptomic and metabolomic analyses. Metabolites. 2025; 15 (10): 647 https://doi.org/10.3390/metabo15100647.

57. Kim M.O., Ryu H.W., Choi J.H., et al. Anti-obesity effects of spiramycin in vitro and in vivo. PLoS One. 2016; 11 (7): e0158632. https://doi.org/10.1371/journal.pone.0158632.

58. Baigozina E.A., Podgurskaya E.P., Senina O.A., et al. Potential for use and clinical efficacy of spiramycin in the empirical treatment of lower respiratory tract infection in present day. Russian Medical Journal. 2024; 1: 47–51.

59. Martin-Loeches I., Torres A., Nagavci В., et al. ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia. Intensive Care Med. 2023; 49 (6): 615–32. https://doi.org/10.1007/s00134-023-07033-8.

60. Kozlov R.S., Ivanchik N.V., Mikotina A.V., Dekhnich A.V. In vitro activity of macrolides against Streptococcus pneumoniae and Streptococcus pyogenes in the Russian Federation: “Status praesens”. Clinical Microbiology and Antimicrobial Chemotherapy. 2024; 26 (3): 318–26 (in Russ.). https://doi.org/10.36488/cmac.2024.3.318-326.

61. Yakovlev S.V., Sidorenko S.V., Rafalsky V.V., Spichak T.V. (Eds.) Strategy and tactics of rational use of antimicrobial agents in outpatient practice: Eurasian clinical guidelines. Moscow: Pre100 Print; 2016: 144 pp. (in Russ.).

62. WHO Model List of Essential Medicines – 23rd list, 2023. Available at: https://www.who.int/publications/i/item/WHO-MHP-HPSEML-2023.02 (accessed 20.11.2025).