In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains

AKTAŞ, Gülseren; DERBENTLİ, Şengül

In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains

Gülseren AKTAŞ, (İstanbul Üniversitesi İstanbul Tıp Fakültesi, Tıbbi Mikrobiyoloji Anabilim Dalı, İstanbul, Türkiye)

Şengül DERBENTLİ (İstanbul Üniversitesi İstanbul Tıp Fakültesi, Tıbbi Mikrobiyoloji Anabilim Dalı, İstanbul, Türkiye)

Kafkas Tıp Bilimleri Dergisi

1 0

Yıl: 2016 Cilt: 6 Sayı: 3 Sayfa Aralığı: 162 - 168 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains

Öz:

AMAÇ: Daptomisinin, rifampisin ve gentamisin ile kombinasyonlarının, hem yüksek düzeyde aminoglikozid direnci (HLAR) olan ve hem de HLAR olmayan (non-HLAR) vankomisine dirençli enterokok (VRE) suşlarına karşı etkinliği in-vitro koşullarda araştırılmıştır.YÖNTEM: Otuz dokuz VRE suşunun laboratuvar tanısı konvansiyonel yöntemler ile yapılmıştır. HLAR araştırması için 120 µg gentamisin ve 300 µg streptomisin içeren diskler kullanılarak yapılan difüzyon yöntemi sonucunda; suşların %41'inin (16/39) gentamisin ve streptomisine yüksek düzeyde dirençli (HLAR) ve %59'unun (23/39) ise duyarlı (non-HLAR) olduğu belirlenmiştir.Çalışmada kullanılan tüm antibiyotiklerin minimum inhibitör konsantrasyon (MİK) değerleri, Clinical and Laboratory Standards Institute (CLSI)'ın önerileri doğrultusunda, buyyonda mikrodilüsyon yöntemi ile belirlenmiş, sonuçları aynı standarda göre değerlendirilmiştir.Antibiyotik kombinasyonlarının in-vitro aktivitesi "checkerboard" mikrodilüsyon tekniği kullanılarak saptanmıştır. Çalışmada kullanılan suşlar için, antibiyotiklerin tek başına ve kombinasyon halinde iken elde edilen MİK değerlerine göre fraksiyonel inhibitör konsantrasyon indeks (FİKİ) değerleri hesaplanmıştır. Buna göre FİKİ <=0,5 olarak bulunan sonuçlar sinerjist; FİKİ >0,5-4,0 additif/indifferens; ve FİKİ >4,0 olarak bulunan sonuçlar ise antagonist etki olarak değerlendirilmiştir.BULGULAR: Suşların tümü (%100) daptomisine duyarlı bulunurken, rifampisine duyarlılık oranı ise %5,1 (2/39) olarak tespit edilmiştir. Daptomisinin, rifampisin ve gentamisin ile kombinasyonları non-HLAR suşlarının sırasıyla %34,8 (8/23) ve %8,7'si (2/23) için sinerjist etkili bulunmasına karşın, suşların çoğunluğu için additif/indifferens etkili saptanmıştır. Daptomisinin rifampisin ile kombinasyonu HLAR suşlarının %50'si (8/16) için sinerjist etkili bulunurken, daptomisinin gentamisin ile kombinasyonunun, suşların hiçbiri için sinerjist etki sağlamadığı gözlenmiştir. Tüm VRE suşları için daptomisin/rifampisin ve daptomisin/gentamisin kombinasyonlarının FİKİ değerleri sırasıyla 0,155-1,5 ve 0,375-2,0 olarak belirlenmiştir. Her iki antibiyotik kombinasyonunun da, çalışmada denenen VRE suşlarının hiçbiri için antagonist etki göstermediği saptanmıştır.SONUÇ: Çalışmanın sonuçları, hem HLAR ve hem de non-HLAR VRE suşları tarafından oluşturulan ciddi VRE enfeksiyonların tedavisinde daptomisin/rifampisin kombinasyonunun önerilebilir bir alternatif olduğu fikrini vermiştir

Anahtar Kelime:

Konular: Genel ve Dahili Tıp

Daptomisinin Rifampisin ve Gentamisin ile Kombinasyonlarının VRE Suşlarına in-vitro Etkinliği

Öz:

AIM: In-vitro activity of daptomycin in combination with rifampicin and gentamicin, was assessed against vancomycin-resistant enterococci (VRE) with both high-level aminoglycoside resistance (HLAR) and non-HLAR.METHODS: Identification of 39 VRE was performed using conventional methods. HLAR strains were identified by using disk diffusion method with gentamicin: 120 µg and streptomycin: 300 µg disks. The rates of HLAR and non-HLAR were established as 41% (16/39) and 59% (23/39), respectively.Minimum inhibitory concentration (MIC) of all antibiotics used were determined and evaluated using microbroth dilution technique as described by Clinical and Laboratory Standards Institute (CLSI). In-vitro activities of antibiotic combinations were determined using microbroth "checkerboard" microdilution technique. Fractional inhibitory concentration index (FICI) were calculated relative to MIC values of antibiotics both alone and in combinations. Synergy was defined as a FICI of <=0.5, additive/indifference as a FICI >0.5-4.0 and antagonism as a FICI of >4.0.RESULTS: All strains were established as daptomycin susceptible (100%) while rifampicin susceptibility rate was found to be 5.1% (2/39) according to MICs. When daptomycin was combined with rifampicin and gentamicin, additive/indifferent effects were observed for the majority of 39 strains, even though the synergistic effect defined in non-HLAR were 34.8% and 8.7%, respectively. Although daptomycin combination with rifampicin showed a synergistic effect against 50% of HLAR, no synergism was observed in combination of daptomycin with gentamicin. The combinations of both daptomycin/rifampicin and daptomycin/gentamicin also showed FICI of 0.155-1.5 and 0.375-2 against strains, respectively. There was no antagonism observed in any of the combinations.CONCLUSION: The results of the study suggest that the combination of daptomycin/rifampicin may be recommended as an alternative in treatment of serious VRE infections caused by both HLAR and non-HLAR

Anahtar Kelime:

Konular: Genel ve Dahili Tıp

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

Kamboj M, Chung D, Seo SK, et al. The changing epidemiology of vancomycin-resistant Enterococcus (VRE) bacteremia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Biol Blood Marrow Transplant 2010;16:1576-81.
Cattaneo C, Casari S, Bracchi F, et al. Recent increase in Enterococci, viridians streptococci, Pseudomonas spp. and multiresistant strains among haematological patients, with a negative impact on outcome. Results of a 3-year surveillance study at a single institution. Scand J Infect Dis 2010;42:324-32.
Pillai SK, Moellering RC Jr, Eliopoulos GM. Antimicrobial combinations, In: Lorian V. editor, Antibiotics in Laboratory Medicine, 5th ed., Philadelphia: Lippincott Williams and Wilkins; 2005:365-440.
Carlet J. Antibiotics must realy be protected. Oudega B. editor, FEMS Affiliates Letter, FEMS, June 2014.
Kristich CJ, Rice LB, Arias CA. Enterococcal infection- treatment and antibiotic resistance. In: Gilmore MS, Clewell DB, Ike Y, Shankar N. editors, Source Enterococci: From commensals to leading causes of drug resistant infection. Boston: Massachusetts Eye and Ear Infirmary, 2014.
Salzer W. Antimicrobial-resistant gram-positive bacteria in PD peritonitis and the newer antibiotics used to treat them. Perit Dial Int 2005;25:313-9.
Hall DH, Steed ME, Arias CA, et al. Evaluation of standard- and high-dose daptomycin versus linezolid against vancomycin- resistant Enterococcus isolates in an in vitro pharmacokinetic/ pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother 2012;56:3174-80.
Steenberger JN, Alder J, Thorne GM, et al. Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram- positive infections. J Antimicrob Chemother 2005;55:283-8.
D'Costa VM, McGrann KM, Hughes DW, et al. Sampling the antibiotic resistome. Science 2006;311:374-7.
Pillai SK, Moellering RC Jr, Eliopoulos GM. Antimicrobial combinations, In: Lorian V editor, Antibiotics in Laboratory Medicine 5th ed. Philadelphia PA. Lippincott Williams and Wilkins; 2005:365-440.
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing 18th Informational supplement M100-S20, CLSI, Wayne, Pa; 2010.
Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically: Approved Guideline, 7. Approved Standard M7-A7, CLSI, Wayne, Pa; 2006.
13. Odds FC. Synerg y, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 2003;52(1):1.
14. Mohr JF, Friedrich LV, Yankelev S, et al. Daptomycin for the treatment of enterococcal bacteraemia: results from the Cubicin Outcomes Registry and Experience (CORE). Int J Antimicrob Agents 2009;33:543-8.
15. Steenbergen JN, Mohr JF, Thorne GM. Effects of daptomycin in combination with other antimicrobial agents: a review of in vitro and animal model studies. J Antimicrob Chemother 2009;64:1130-8.
16. Rice LB, Bonomo RA. Genetic and biochemical mechanisms of bacterial resistance to antimicrobial agents. In: Lorian V. editor, Antibiotics in laboratory medicine 5th ed. Lippincott Williams and Wilkins: Philadelphia PA; 2005:441-508.
17. Rand KH, Houck H. Daptomycin synerg y with rifampicin and ampicillin against vancomycin-resistant enterococci. J Antimicrob Chemother 2004;53:530-2.
18. Holmberg A, Rasmussen M. Antibiotic regimens with rifampicin for treatment of Enterococcus faecium in biofilms. Int J Antimicrob Agents 2014;44:78-80.
19. Horodniceanu T, Bougueleret L, El-Solh N, et al. High-level, plasmid-borne resistance to gentamicin in Streptococcus faecalis subsp. Zymogeses. Antimicrob Agents Chemother 1979;16:686-9.
20. Leclercq R, Dutka-Malen S, Brisson Noel A, et al. Resistance of enterococci to aminoglycosides and glycopeptides. Clin Infect Dis 1992;15:495-501.
21. Snydman DR, McDermott LA, Jacobus NV. Evaluation of in vitro interaction of daptomycin with gentamicin or beta-lactam antibiotics against Staphylococcus aureus and enterococci by FIC index and timed-kill curves. J Chemother 2005;17:614-21.
22. Luther MK, Arvanitis M, Mylonakis E, et al. Activity of daptomycin or linezolid in combination with rifampin or gentamicin against biofilm-forming Enterococcus faecalis or E. faecium in an in vitro pharmacodynamic model using simulated endocardial vegetations and an in vivo survival assay using Galleria mellonella larvae. Antimicrob Agents Chemother 2014;58:4612-20.
23. DeRyke CA, Sutherland C, Zhang B, et al. Serum bactericidal activities of high-dose daptomycin with and without coadministration of gentamicin against isolates of Staphylococcus aureus and Enterococcus species. Antimicrob Agents Chemother 2006;50:3529-34.

APA	AKTAŞ G, DERBENTLİ Ş (2016). In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. , 162 - 168.
Chicago	AKTAŞ Gülseren,DERBENTLİ Şengül In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. (2016): 162 - 168.
MLA	AKTAŞ Gülseren,DERBENTLİ Şengül In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. , 2016, ss.162 - 168.
AMA	AKTAŞ G,DERBENTLİ Ş In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. . 2016; 162 - 168.
Vancouver	AKTAŞ G,DERBENTLİ Ş In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. . 2016; 162 - 168.
IEEE	AKTAŞ G,DERBENTLİ Ş "In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains." , ss.162 - 168, 2016.
ISNAD	AKTAŞ, Gülseren - DERBENTLİ, Şengül. "In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains". (2016), 162-168.

APA	AKTAŞ G, DERBENTLİ Ş (2016). In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. Kafkas Tıp Bilimleri Dergisi, 6(3), 162 - 168.
Chicago	AKTAŞ Gülseren,DERBENTLİ Şengül In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. Kafkas Tıp Bilimleri Dergisi 6, no.3 (2016): 162 - 168.
MLA	AKTAŞ Gülseren,DERBENTLİ Şengül In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. Kafkas Tıp Bilimleri Dergisi, vol.6, no.3, 2016, ss.162 - 168.
AMA	AKTAŞ G,DERBENTLİ Ş In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. Kafkas Tıp Bilimleri Dergisi. 2016; 6(3): 162 - 168.
Vancouver	AKTAŞ G,DERBENTLİ Ş In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains. Kafkas Tıp Bilimleri Dergisi. 2016; 6(3): 162 - 168.
IEEE	AKTAŞ G,DERBENTLİ Ş "In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains." Kafkas Tıp Bilimleri Dergisi, 6, ss.162 - 168, 2016.
ISNAD	AKTAŞ, Gülseren - DERBENTLİ, Şengül. "In-vitro Activities of Daptomycin in Combination with Rifampicin and Gentamicin Against VRE Strains". Kafkas Tıp Bilimleri Dergisi 6/3 (2016), 162-168.