Nowe aspekty mikrobiologiczne fosfomycyny

New microbiological aspects of fosfomycin

María Díez-Aguilar, Rafael Cantón

Servicio de Microbiología. Hospital Universitario Ramón y Cajal e Instituto Ramón y Cajal de Investigación Sanitaria  (IRYCIS). Madryt. Red Española de Investigación en Patología Infecciosa (REIPI).

Rafael Cantón
Servicio de Microbiología. Hospital Universitario Ramón y Cajal e Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Madryt. Red Española de Investigación en Patología Infecciosa (REIPI)
rafael.canton@salud.madrid.org

Cytowanie / Citation

Tekst stanowi tłumaczenie artykułu „Nuevos aspectos microbiológicos de la fosfomicina” opublikowanego w czasopiśmie „Revista Española de Quimioterapia” autorstwa María Díez-Aguilar i Rafael Cantón.
Rev Esp Quimioter 2019;32(Suppl 1):8–18
Rozpowszechniany na podstawie licencji „Uznanie autorstwa 4.0 Międzynarodowe (CC BY 4.0)”
Copyright ©2019 María Díez-Aguilar, Rafael Cantón

Tłumaczenie oraz publikacja w czasopiśmie „Zakażenia XXI wieku” za zgodą wydawcy: Sociedad Española de Quimioterapia
Zakażenia XXI wieku 2019;2(5):205–216.
doi: 10.31350/zakazenia/2019/5/Z2019040

Wersja elektroniczna / Article ePDF

Streszczenie:
Odkrycie fosfomycyny ponad 40 lat temu było ważnym kamieniem milowym w antybiotykoterapii. Przydatność tego antybiotyku – w monoterapii lub w leczeniu skojarzonym – w terapii zakażeń wywołanych przez drobnoustroje wielolekooporne jest obecnie bardziej oczywista niż kiedykolwiek wcześniej. Europejska Agencja Leków i amerykańska Agencja ds. Żywności i Leków zainicjowały procesy przeglądu zebranych informacji na temat zastosowania fosfomycyny oraz danych z nowych badań klinicznych dotyczących tego związku. Celem agencji jest ustalenie wspólnych kryteriów stosowania leku w Europie oraz dopuszczenie fosfomycyny do obrotu w USA. Mechanizm działania fosfomycyny powoduje brak oporności krzyżowej z innymi antybiotykami. Opisano jednak różne mechanizmy oporności na fosfomycynę, a najważniejszym z nich z punktu widzenia epidemiologicznego jest inaktywacja enzymatyczna, która zasadniczo jest związana z genem fosA3 przenoszonym przez plazmid. Fosfomycynę stosowano częściej w Azji w zakażeniach pałeczkami z rzędu Enterobacterales wytwarzających beta-laktamazę o rozszerzonym spektrum oraz wytwarzających karbapenemazę. Pomimo że fosfomycyna wykazuje niższą naturalną aktywność względem Pseudomonas aeruginosa niż względem Escherichia coli, udowodniono jej aktywność w biofilmach, zwłaszcza w kombinacji z aminoglikozydami. Obecne umieszczenie fosfomycyny w arsenale terapeutycznym do leczenia zakażeń wywołanych przez drobnoustroje wielolekooporne wymaga podjęcia nowych wysiłków mających na celu lepsze poznanie tego związku, również w zakresie metod laboratoryjnych wykorzystywanych w badaniu wrażliwości na antybiotyki.

Słowa kluczowe: fosfomycyna, mechanizmy oporności, badanie wrażliwości, biofilmy, kombinacje przeciwdrobnoustrojowe

Abstract:
The discovery of fosfomycin more than 40 years ago was an important milestone in antibiotic therapy. The antibiotic’s usefulness, alone or in combination, for treating infections caused by multidrug-resistant microorganisms is clearer than ever. Both the European Medicines Agency and the US Food and Drug Administration have open processes for reviewing the accumulated information on the use of fosfomycin and the information from new clinical trials on this compound. The agencies’ objectives are to establish common usage criteria for Europe and authorize the sale of fosfomycin in the US, respectively. Fosfomycin’s single mechanism of action results in no cross-resistance with other antibiotics. However, various fosfomycin-resistance mechanisms have been described, the most important of which, from the epidemiological standpoint, is enzymatic inactivation, which is essentially associated with a gene carrying a fosA3-harboring plasmid. Fosfomycin has been found more frequently in Asia in extended-spectrum beta-lactamase-producing and carbapenemase-producing Enterobacterales. Although fosfomycin presents lower intrinsic activity against Pseudomonas aeruginosa compared with that presented against Escherichia coli, fosfomycin’s activity has been demonstrated in biofilms, especially in combination with aminoglycosides. The current positioning of fosfomycin in the therapeutic arsenal for the treatment of infections caused by multidrug-resistant microorganisms requires new efforts to deepen our understanding of this compound, including those related to the laboratory methods employed in the antimicrobial susceptibility testing study.

Key words: fosfomycin, mechanisms of resistance, susceptibility testing study, biofilms, antimicrobial combinations

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Konflikt interesów: RC has participated in training activities organized by ERN, Pfizer and MDS.
Potential conflicts of interest: RC has participated in training activities organized by ERN, Pfizer and MDS.