Dlaczego wankomycyna nie jest właściwym wyborem w leczeniu zakażeń skóry i tkanek miękkich?

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DLACZEGO WANKOMYCYNA NIE JEST WŁAŚCIWYM WYBOREM

W LECZENIU ZAKAŻEŃ SKÓRY I TKANEK MIĘKKICH?

WHY IS VANCOMYCIN NOT THE RIGHT CHOICE FOR THE TREATMENT OF SKIN AND SOFT TISSUE

INFECTIONS?

Katedra i Zakład Mikrobiologii Farmaceutycznej i Parazytologii, Uniwersytet Medyczny we Wrocławiu, ul. Borowska 211a, 50-556 Wrocław, Tel.: 71 784 05 11, e-mail: beata.kowalska-krochmal @umed.wroc.pl Wpłynęło: 03.08.2018 Zaakceptowano: 10.08.2018 DOI: dx.doi.org/10.15374/FZ2018039

STRESZCZENIE: Celem pracy było przedstawienie przyczyn ograniczonej skuteczności lub na-wet braku skuteczności wankomycyny w terapii zakażeń skóry i tkanek miękkich (SSTI), w tym zakażeń ostrych (ABSSSI), wywołanych przez S. aureus, oraz określenie najskuteczniejszych opcji terapeutycznych. Zwrócono uwagę na spadek stopnia wrażliwości S. aureus na wanko-mycynę, słabą penetrację tego glikopeptydu do skóry i tkanek miękkich, a także wysokie ryzy-ko powikłań, do których zalicza się jego toksyczne działanie na nerki. Jaryzy-ko alternatywę dla wan-komycyny wyszczególniono nowy lipoglikopeptyd – dalbawancynę, której skuteczność wo-bec zakażeń ABSSSI wywołanych przez S. aureus jest nie gorsza niż w przypadku zastosowania linezolidu czy kombinacji wankomycyna/linezolid, a farmakokinetyka jest zdecydowanie lep-sza. Możliwość leczenia z użyciem jednej lub maksymalnie dwóch dawek dalbawancyny po-zwala na osiągnięcie efektu klinicznego przy znacznym ograniczeniu pobytu pacjenta w szpi-talu oraz kosztów i niepożądanych zdarzeń związanych z wydłużoną hospitalizacją.

SŁOWA KLUCZOWE: ABSSSI, dalbawancyna, wankomycyna

ABSTRACT: The paper presents the reasons for the limited or even lack of efficiency of vanco-mycin in skin and soft tissue infections (SSTI – skin and soft tissue infections), including acute skin and soft tissue infections (ABSSSI) caused by S. aureus, and thus the basis for the choice of more effective treatment options in such infections. The decrease of the level of susceptibility of S.aureus to vancomycin, the poor penetration of this glycopeptide into the skin and soft tis-sues and the high risk of side effects, including those toxic to the kidneys, have been noted. As an alternative to vancomycin, a new lipoglycopeptide – dalbavancin was specified, whose effi-ciency against infections caused by S. aureus is no worse than linezolid or vancomycin/linezo-lid combinations, and the pharmacokinetic parameters are satisfactory. The possibility of treat-ment with one or two doses of dalbavancin can enable to achieve a clinical effect with a signi-ficant reduction in the patient’s stay in the hospital as well as costs and adverse events associa-ted with prolonged hospitalization.

KEY WORDS: ABSSSI, dalbavancin, vancomycin

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Antybiotyki aktywne wobec

MSSA MRSA Penicyliny izoksazolylowe, np. kloksacylina Wankomycyna Cefazolina Oritawancyna Cefaleksyna Ceftarolina Klindamycyna Kotrymoksazol Kotrymoksazol Daptomycyna Doksycyklina Tedizolid Linezolid Dalbawancyna

Tabela 1. Antybiotyki rekomendowane w zakażeniach skóry i tkanek miękkich wywołanych przez metycylinowrażliwe (MSSA) i metycylino-oporne (MRSA) szczepy S. aureus [3, 5, 14].

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Charakterystyka farmakologiczna

Parametry Wankomycyna Dalbawancyna Źródło

MIC₉₀ (μg/ml) 2 0,03 [20]

Droga podania _i.v. _i.v. [27]

Dawkowanie 1 g co 12 godzin/10–14 dni Jedna dawka 1500 mg

lub 2 dawki: 1000 mg i po 7 dniach 500 mg [27, 30] Wiązanie z białkami 55% 93% [32] T_1/2 4–6 godzin 346 godzin [30–33] Vd 0,4–1 l/kg 15,7 l po podaniu 1000 mg [33, 34]

Lipo-/hydrofilność Hydrofilny Hydrofilny [26]

Sposób działania Bakteriobójczy Bakteriobójczy [26, 27]

Penetracja do tka-nek miękkich 10–30% stężenia w surowicy 60% w płynie pęcherzo-wym [23, 28, 33, 35] Wewnątrzkomórko-wa penetracja Nikła Średnia [28, 33, 36]

Pk/PD AUC₂₄/MIC ≥400 AUC/MIC T >MIC

[21, 28, 34]

Nefrotoksyczność Wysoka Niska [21, 25, 26, 27]

Konieczność modyﬁkacji dawek w przypadku:

Niewydolności nerek Tak Nie (przy Cl ≥30 mg/l) [26, 27]

W otyłości Tak Nie [37]

Tabela 2. Wybrane parametry farmakologiczne wankomycyny i dalbawancyny.

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KONFLIKT INTERESÓW: nie zgłoszono.

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