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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Consilium Medicum</journal-id><journal-title-group><journal-title xml:lang="en">Consilium Medicum</journal-title><trans-title-group xml:lang="ru"><trans-title>Consilium Medicum</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>Consilium Medicum</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2075-1753</issn><issn publication-format="electronic">2542-2170</issn><publisher><publisher-name xml:lang="en">Consilium Medicum</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">627435</article-id><article-id pub-id-type="doi">10.26442/20751753.2023.7.202284</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Статьи</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Fosfomycin: An old antibiotic and new perspectives. A review</article-title><trans-title-group xml:lang="ru"><trans-title>Фосфомицин: старый антибиотик и новые перспективы. Обзор литературы</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8228-1114</contrib-id><contrib-id contrib-id-type="scopus">7004151126</contrib-id><name-alternatives><name xml:lang="en"><surname>Leonova</surname><given-names>Marina V.</given-names></name><name xml:lang="ru"><surname>Леонова</surname><given-names>Марина Васильевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>D. Sci. (Med.), Prof., Corr. Memb. RANS</p></bio><bio xml:lang="ru"><p>чл.-кор. РАЕН, д-р мед. наук, проф., клинический фармаколог</p></bio><email>anti23@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Interregional Public Organization "Association of Clinical Pharmacologists"</institution></aff><aff><institution xml:lang="ru">Межрегиональная общественная организация «Ассоциация клинических фармакологов России»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2023-07-15" publication-format="electronic"><day>15</day><month>07</month><year>2023</year></pub-date><volume>25</volume><issue>7</issue><issue-title xml:lang="en">Urology</issue-title><issue-title xml:lang="ru">Урология</issue-title><fpage>433</fpage><lpage>438</lpage><history><date date-type="received" iso-8601-date="2024-02-24"><day>24</day><month>02</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2024-02-24"><day>24</day><month>02</month><year>2024</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2023, Consilium Medicum</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2023, ООО "Консилиум Медикум"</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="en">Consilium Medicum</copyright-holder><copyright-holder xml:lang="ru">ООО "Консилиум Медикум"</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-sa/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://consilium.orscience.ru/2075-1753/article/view/627435">https://consilium.orscience.ru/2075-1753/article/view/627435</self-uri><abstract xml:lang="en"><p>Urinary tract infection (UTI) is one of the most common urological diseases and presents a problem for rational antibiotic therapy due to the growing antibiotic resistance. Fosfomycin is one of the older low molecular weight, broad-spectrum bactericidal antibiotics with activity against uropathogens, particularly <italic>Escherichia coli </italic>and others. Fosfomycin is administered as a single dose that achieves very high concentrations of the antibiotic in the urine and bladder, sufficient to eliminate most common uropathogens, including those with multidrug resistance (MDR). Many factors have contributed to the persistence of fosfomycin's antibacterial activity, including the use of a single dose, limited use for UTIs only, and very high and persistent urinary concentrations that rapidly kill bacteria, reducing the possibility of mutant selection. In addition to its antimicrobial properties, fosfomycin has an immunomodulatory effect by altering the function of lymphocytes, monocytes, and neutrophils. It affects the acute inflammatory cytokine response. New data have been obtained on the activity of fosfomycin against biofilms formed by uropathogens and against biofilm-associated bacterial strains with MDR. A new 2020 meta-analysis compared the efficacy of fosfomycin with equivalent antibiotics (β-lactams/cephalosporins, quinolones, sulfonamides, nitrofurantoin) in women in the broad categories of uncomplicated UTI or asymptomatic bacteriuria and found no difference in clinical and microbiological cure rates with comparison groups. A number of other studies in patients with UTIs with MDR or complicated course also showed a high sensitivity of uropathogens to fosfomycin and the effectiveness of treatment with multiple doses (2–3 doses with an interval of 48–72 hrs). Fosfomycin is being considered as a potentially useful antibiotic for the treatment of prostatitis. Current data indicate that sufficient concentrations in prostate tissue are achieved after a single dose of fosfomycin. Recent reviews in 2019 and 2022 present results of studies of fosfomycin for the prevention of infectious complications after transurethral prostate biopsy and in patients with chronic bacterial prostatitis whose pathogens are resistant to other antibiotics. Thus, the accumulation of new scientific data on the mechanisms of action and resistance of fosfomycin reveals more potential advantages of its practical application.</p></abstract><trans-abstract xml:lang="ru"><p>Инфекция мочевыводящих путей (ИМП) является одним из наиболее частых урологических заболеваний и представляет проблему рациональной антибактериальной терапии в связи с растущей антибиотикорезистентностью. Фосфомицин – один из старых низкомолекулярных бактерицидных антибиотиков широкого спектра действия с активностью в отношении уропатогенов, в частности <italic>Escherichia coli</italic> и др. Фосфомицин применяется однократной дозой, которая достигает очень высокой концентрации антибиотика в моче и мочевом пузыре, достаточной для элиминации большинства распространенных уропатогенов, в том числе со множественной лекарственной устойчивостью (МЛУ). Многие факторы способствовали сохранению антибактериальной активности фосфомицина, включая использование однократной дозы, ограниченное применение только для ИМП, очень высокие и устойчивые концентрации в моче, которые быстро убивают бактерии, уменьшая возможность селекции мутантов. В дополнение к антимикробным свойствам фосфомицин оказывает иммуномодулирующее действие, изменяя функцию лимфо-, моноцитов и нейтрофилов. Он влияет на острую воспалительную цитокиновую реакцию. Получены новые данные по активности фосфомицина в борьбе против биопленок, образованных уропатогенами, и в отношении ассоциированных с биопленкой штаммов бактерий с МЛУ. В новых метаанализах 2020 г. сравнивали эффективность фосфомицина с эквивалентными антибиотиками (β-лактамами/цефалоспоринами, хинолонами, сульфаниламидами, нитрофурантоином) у женщин в широких категориях – с неосложненной ИМП или бессимптомной бактериурией – и не выявили различий по частоте клинического и микробиологического излечения с группами сравнения. В ряде других исследований у пациентов с ИМП с МЛУ или осложненным течением также показана высокая чувствительность уропатогенов к фосфомицину и эффективность лечения c применением многократных доз (2–3 дозы с интервалом 48–72 ч). Фосфомицин рассматривается как потенциально полезный антибиотик для лечения простатита. Современные данные свидетельствуют о том, что после однократной дозы фосфомицина достигаются достаточные концентрации в ткани предстательной железы. В недавних обзорах 2019 и 2022 г. представлены результаты исследований применения фосфомицина для профилактики инфекционных осложнений после трансуретральной биопсии простаты, а также у пациентов с хроническим бактериальным простатитом, возбудители которых резистентны к другим антибиотикам. Таким образом, накопление новых научных данных о механизмах действия и резистентности фосфомицина увеличивает возможности его практического применения.</p></trans-abstract><kwd-group xml:lang="en"><kwd>fosfomycin</kwd><kwd>resistance</kwd><kwd>biofilms</kwd><kwd>urinary tract infections</kwd><kwd>cystitis</kwd><kwd>prostatitis</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>фосфомицин</kwd><kwd>резистентность</kwd><kwd>биопленки</kwd><kwd>инфекции мочевых путей</kwd><kwd>цистит</kwd><kwd>простатит</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Falagas ME, Vouloumanou EK, Samonis G, Vardakas KZ. Fosfomycin. Clin Microbiol Rev. 2016;29(2):321-47. DOI:10.1128/CMR.00068-15</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Castañeda-García A, Blázquez J, Rodríguez-Rojas A. Molecular mechanisms and clinical impact of acquired and intrinsic fosfomycin resistance. Antibiotics (Basel). 2013;2(2):217-36. DOI:10.3390/antibiotics2020217</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Schito GC. Why fosfomycin trometamol as first line therapy for uncomplicated UTI? Int J Antimicrob Agents. 2003;22 Suppl. 2:79-83. DOI:10.1016/s0924-8579(03)00231-0</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Silver LL. Fosfomycin: Mechanism and resistance. Cold Spring Harb Perspect Med. 2017;7(2):a025262. DOI:10.1101/cshperspect.a025262</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Patel SS, Balfour JA, Bryson HM. Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections. Drugs. 1997;53(4):637-56. DOI:10.2165/00003495-199753040-00007</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Keating GM. Fosfomycin trometamol: A review of its use as a single-dose oral treatment for patients with acute lower urinary tract infections and pregnant women with asymptomatic bacteriuria. Drugs. 2013;73(17):1951-66. DOI:10.1007/s40265-013-0143-y</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Zamani H, Salehzadeh A. Biofilm formation in uropathogenic Escherichia coli: Association with adhesion factor genes. Turk J Med Sci. 2018;48(1):162-7. DOI:10.3906/sag-1707-3</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Soto SM. Importance of biofilms in urinary tract infections: New therapeutic approaches. Adv Biol. 2014;543974. DOI:10.1155/2014/543974</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Gajdács M, Kárpáti K, Nagy ÁL, et al. Association between biofilm-production and antibiotic resistance in Escherichia coli isolates: A laboratory-based case study and a literature review. Acta Microbiol Immunol Hung. 2021. DOI:10.1556/030.2021.01487</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Anderson GG, Palermo JJ, Schilling JD, et al. Intracellular bacterial biofilm-like pods in urinary tract infections. Science. 2003;301(5629):105-7. DOI:10.1126/science.1084550</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Zhao F, Yang H, Bi D, et al. A systematic review and meta-analysis of antibiotic resistance patterns, and the correlation between biofilm formation with virulence factors in uropathogenic E. coli isolated from urinary tract infections. Microb Pathog. 2020;144:104196. DOI:10.1016/j.micpath.2020.104196</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Garousi M, Monazami Tabar S, Mirazi H, et al. A global systematic review and meta-analysis on correlation between biofilm producers and non-biofilm producers with antibiotic resistance in uropathogenic Escherichia coli. Microb Pathog. 2022;164:105412. DOI:10.1016/j.micpath.2022.105412</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>González MJ, Da Cunda P, Notejane M, et al. Fosfomycin tromethamine activity on biofilm and intracellular bacterial communities produced by uropathogenic Escherichia coli isolated from patients with urinary tract infection. Pathog Dis. 2019;77(3):ftz022. DOI:10.1093/femspd/ftz022</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Dzib-Baak HE, Uc-Cachón AH, Dzul-Beh AJ, et al. Efficacy of fosfomycin against planktonic and biofilm-associated MDR uropathogenic Escherichia coli clinical isolates. Trop Med Infect Dis. 2022;7(9):235. DOI:10.3390/tropicalmed7090235</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Falagas ME, Maraki S, Karageorgopoulos DE, et al. Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae isolates to fosfomycin. Int J Antimicrob Agents. 2010;35(3):240-3. DOI:10.1016/j.ijantimicag.2009.10.019</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Mezzatesta ML, La Rosa G, Maugeri G, et al. In vitro activity of fosfomycin trometamol and other oral antibiotics against multidrug-resistant uropathogens. Int J Antimicrob Agents. 2017;49(6):763-6. DOI:10.1016/j.ijantimicag.2017.01.020</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Falagas ME, Vouloumanou EK, Togias AG, et al. Fosfomycin versus other antibiotics for the treatment of cystitis: A meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2010;65(9):1862-77. DOI:10.1093/jac/dkq237</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Gupta K, Hooton TM, Naber KG, et al.; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-20. DOI:10.1093/cid/ciq257</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Cai T, Tamanini I, Tascini C, et al. Fosfomycin trometamol versus comparator antibiotics for the treatment of acute uncomplicated urinary tract infections in women: A systematic review and meta-analysis. J Urol. 2020;203(3):570-8. DOI:10.1097/JU.0000000000000620</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Wang T, Wu G, Wang J, et al. Comparison of single-dose fosfomycin tromethamine and other antibiotics for lower uncomplicated urinary tract infection in women and asymptomatic bacteriuria in pregnant women: A systematic review and meta-analysis. Int J Antimicrob Agents. 2020;56(1):106018. DOI:10.1016/j.ijantimicag.2020.106018</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Trevino SE, Babcock HM, Henderson JP, et al. Perceptions and behaviours of infectious diseases physicians when managing urinary tract infections due to MDR organisms. J Antimicrob Chemother. 2015;70(12):3397-400. DOI:10.1093/jac/dkv271</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Neuner EA, Sekeres J, Hall GS, van Duin D. Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother. 2012;56(11):5744-8. DOI:10.1128/AAC.00402-12</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Seroy JT, Grim SA, Reid GE, et al. Treatment of MDR urinary tract infections with oral fosfomycin: A retrospective analysis. J Antimicrob Chemother. 2016;71(9):2563-8. DOI:10.1093/jac/dkw178</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Qiao LD, Zheng B, Chen S, et al. Evaluation of three-dose fosfomycin tromethamine in the treatment of patients with urinary tract infections: An uncontrolled, open-label, multicentre study. BMJ Open. 2013;3(12):e004157. DOI:10.1136/bmjopen-2013-00415</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Giancola SE, Mahoney MV, Hogan MD, et al. Assessment of fosfomycin for complicated or multidrug-resistant urinary tract infections: Patient characteristics and outcomes. Chemotherapy. 2017;62(2):100-4. DOI:10.1159/000449422</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Matthews PC, Barrett LK, Warren S, et al. Oral fosfomycin for treatment of urinary tract infection: a retrospective cohort study. BMC Infect Dis. 2016;16(1):556. DOI:10.1186/s12879-016-1888-1</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Konwar M, Gogtay NJ, Ravi R, et al. Evaluation of efficacy and safety of fosfomycin versus nitrofurantoin for the treatment of uncomplicated lower urinary tract infection (UTI) in women – a systematic review and meta-analysis. J Chemother. 2022;34(3):139-48. DOI:10.1080/1120009X.2021.1938949</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Derington CG, Benavides N, Delate T, Fish DN. Multiple-dose oral fosfomycin for treatment of complicated urinary tract infections in the outpatient setting. Open Forum Infect Dis. 2020;7(2):ofaa034. DOI:10.1093/ofid/ofaa034</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Huttner A, Kowalczyk A, Turjeman A, et al. Effect of 5-day nitrofurantoin vs single-dose fosfomycin on clinical resolution of uncomplicated lower urinary tract infection in women: A randomized clinical trial. JAMA. 2018;319(17):1781-9. DOI:10.1001/jama.2018.3627</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Ten Doesschate T, van Haren E, Wijma RA, et al. The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function. Clin Microbiol Infect. 2020;26(10):1355-60. DOI:10.1016/j.cmi.2020.03.001</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Soto SM, Smithson A, Martinez JA, et al. Biofilm formation in uropathogenic Escherichia coli strains: relationship with prostatitis, urovirulence factors and antimicrobial resistance. J Urol. 2007;177(1):365-8. DOI:10.1016/j.juro.2006.08.081</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Gardiner BJ, Mahony AA, Ellis AG, et al. Is fosfomycin a potential treatment alternative for multidrug-resistant gram-negative prostatitis? Clin Infect Dis. 2014;58(4):e101-5. DOI:10.1093/cid/cit704</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Ongün S, Aslan G, Avkan-Oguz V. The effectiveness of single-dose fosfomycin as antimicrobial prophylaxis for patients undergoing transrectal ultrasound-guided biopsy of the prostate. Urol Int. 2012;89(4):439-44. DOI:10.1159/000342370</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Zhanel GG, Zhanel MA, Karlowsky JA. Oral fosfomycin for the treatment of acute and chronic bacterial prostatitis caused by multidrug-resistant Escherichia coli. Can J Infect Dis Med Microbiol. 2018;2018:1404813. DOI:10.1155/2018/1404813</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Marino A, Stracquadanio S, Bellanca CM, et al. Oral fosfomycin formulation in bacterial prostatitis: New role for an old molecule-brief literature review and clinical considerations. Infect Dis Rep. 2022;14(4):621-34. DOI:10.3390/idr14040067</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Los-Arcos I, Pigrau C, Rodríguez-Pardo D, et al. Long-term fosfomycin-tromethamine oral therapy for difficult-to-treat chronic bacterial prostatitis. Antimicrob Agents Chemother. 2016;60:1854-8. DOI:10.1128/AAC.02611-15</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Karaiskos I, Galani L, Sakka V, et al. Oral fosfomycin for the treatment of chronic bacterial prostatitis. J Antimicrob Chemother. 2019;74:1430-7. DOI:10.1093/jac/dkz015</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Bouiller K, Zayet S, Lalloz PE, et al. Efficacy and safety of oral fosfomycin-trometamol in male urinary tract infections with multidrug-resistant Enterobacterales. Antibiotics. 2022;11:198. DOI:10.3390/antibiotics11020198</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Magri V, Boltri M, Cai T, et al. Multidisciplinary approach to prostatitis. Arch Ital Urol Androl. 2019;90(4):227-48. DOI:10.4081/aiua.2018.4.227</mixed-citation></ref></ref-list></back></article>
