HAYRUNİSA HANCI, M. Hamidullah UYANIK, Dilek BİLİCİ, Ahmet AYYILDIZ, AYŞE ALBAYRAK

Klinik örneklerden izole edilen metisiline dirençli stafilokok suşlarında daptomisin etkinliğinin araştırılması

Dünya genelinde Gram pozitif bakterilerden kaynaklanan infeksiyonların insidansı giderek artmaktadır. Gerek toplum gerekse hastane kaynaklı olsun metisiline dirençli stafilokoklara bağlı infeksiyonlar önemli problemlere neden olmaktadır. Hücre duvarı inhibitörü olan daptomisinin etkinliği Gram pozitif bakterilerle sınırlı olup, dirençli bakterilere oldukça etkilidir. Bu çalışmada hastanemize gelen çeşitli klinik materyallerden izole edilen 58 metisiline dirençli Staphylococcus aureus (MRSA) ve kan kültürlerinden izole edilen 29 metisiline dirençli koagülaz negatif stafilokok (MRKNS) suşu çalışma kapsamına alınmıştır. Daptomisin minimum inhibitör konsantrasyon (MİK) değerleri üretici firmanın önerileri doğrultusunda E-test (AB Biodisk, Solna, Sweden) metoduyla saptanmış ve Clinical and Laboratory Standards Institute (CLSI) eşik değerlerine göre yorumlanmıştır. MİK değeri ≥ 1 μg/ml olan suşlar daptomisine dirençli olarak değerlendirilmiştir. Suşların diğer antibiyotiklere duyarlılıkları ise CLSI önerileri doğrultusunda Kirby-Bauer disk difüzyon yöntemiyle saptanmıştır. Bütün suşlar daptomisine duyarlı olarak bulunmuştur. MİK değerleri hem MRSA hem de MRKNS suşları için MİK50 0.125, MİK90 0.25 olarak saptanmıştır. Linezolide direnç tespit edilmemiştir. MRKNS suşlarında eritromisin, MRSA suşlarında ise ofloksasin ve gentamisin en etkisiz antibiyotikler olarak belirlenmiştir. Sonuç olarak daptomisinin hem MRSA hem de MRKNS suşlarında oldukça etkin in-vitro aktiviteye sahip olduğu saptanmıştır. Hastanemizdeki metisiline dirençli stafilokok infeksiyonlarının antimikrobiyal tedavisinde daptomisinin iyi bir alternatif olabileceğini düşünmekteyiz.

Investigation of Daptomycin Activity Against Methicillin Resistant Staphylococci Isolated from Clinical Samples

The incidence of infections caused by Gram positive microorganisms is increasing all over the world. Methicillin resistant staphylococcal infections have been important problem both in nosocomial and community acquired infections. Daptomycin, a cell wall-inhibiting antibiotic with a spectrum of activity limited to Gram positive bacteria, has also been demonstrated to have activity against resistant bacteria. Fifty-eight methicillin resistant Staphylococcus aureus (MRSA) isolated from various clinical samples and 29 methi- cillin resistant coagulase negative Staphylococcus (MRCoNS) isolated from blood cultures were included to this study. Daptomycin susceptibilities were determined by E-test (AB Biodisk, Solna, Sweden) according to the manufacturers recommendations and results were evaluated by the Clinical and Laboratory Standards Institute (CLSI) criteria. If minimal inhibition concentration (MIC) value ≥ 1 μg/ml, we evaluated that daptomycin resistant strain. Susceptibilities to other antibiotics were determined by Kirby-Bauer disc diffusion method according to CLSI standards. All of the isolates were susceptible to daptomycin. The MIC values for both MRSA and MRCoNS isolates were MIC50 0.125, MIC90 0.25. There was no resistance to linezolid. Erythromycin was the most ineffective antibiotic for MRCoNS strains, ofloxacin and gentamicin were the most ineffective antibiotics for MRSA strains. As a result, daptomycin showed in-vitro effective activity against both MRSA and MRCoNS strains. Daptomycin may be a good alternative agent for the antimicrobial therapy of infections due to methicillin resistant staphylococcal infections in our hospital.

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Alves dAzevedo P, Comin G, Cantarelli V. Characterization of a new coagulase-negative Staphylococcus species (Staphylococcus pettenko- feri) isolated from blood cultures from a hospitali- zed patient in Porto Alegre, Brazil, Revista da Sociedade Brasileira de Medicina Tropical 2010;43(2): 331-2. http://dx.doi.org/10.1590/S0037-86822010000300023
Arbeit RD, Maki D, Tally FP, Campanaro E, Eisenstein BI. Daptomycin 98-01 and 99-01 Investigators. The safety and efficacy of daptomycin for the treatment of complicated skin and skin structure infections, Clin Infect Dis 2004;38(12): 1673-81. http://dx.doi.org/10.1086/420818 PMid:15227611
Arslan H, Azap ÖK, Ergin F, Karaman SÖ, Oruç E. In vitro activity of daptomycin against isolates of Staphylococcus aureus and enterococci: first results from Turkey, Letters / Int J Antimicrob Agents 2004;23(6):642-3. http://dx.doi.org/10.1016/j.ijantimicag.2004.03.010 PMid:15194140
Bell JM, Turnidge JD, Sader HS, Jones RN. Antimicrobial activity and spectrum of daptomycin: results from the surveillance program in Australia and New Zealand (2008), Pathology 2010;42(5):470-3. http://dx.doi.org/10.3109/00313025.2010.493869 PMid:20632825
Bhavnani SM, Prakhya A, Hammel JP, Ambrose PG. Cost-effectiveness of daptomycin versus vancomycin and gentamicin for patients with methicillin-resistant Staphylococcus aureus bacteremia and/or endocarditis, Clin Infect Dis 2009; 49(5):691-8. http://dx.doi.org/10.1086/604710 PMid:19635023
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; Twenty- second informational supplement, M100- S22, CLSI, Wayne, PA (2012).
Finney MS, Crank CW, Segreti J. Use of daptomycin to treat drug resistant Gram-positive bone and joint infections, Curr Med Res Opin 2005;21(12): 1923-6. http://dx.doi.org/10.1185/030079905X74961 PMid:16368041
Fowler VG Jr, Boucher HW, Corey GR et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus, N Engl J Med 2006;355(7):653-65. http://dx.doi.org/10.1056/NEJMoa053783 PMid:16914701
Hayden MK, Rezai K, Hayes RA, Lolans K, Quinn JP, Weinstein RA. Development of daptomycin resistance in vivo in methicillin-resistant Staphylococcus aureus, J Clin Microbiol 2005; 43(10):5285-7. http://dx.doi.org/10.1128/JCM.43.10.5285-5287.2005 PMid:16207998 PMCid:1248493
Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting, Am J Infect Control 2008;36(5):309-32. http://dx.doi.org/10.1016/j.ajic.2008.03.002 PMid:18538699
Huang YC, Chen CJ. Community-associated meticillin-resistant Staphylococcus aureus in children in Taiwan, 2000s, Int J Antimicrob Agents 2011;38(1):2-8. http://dx.doi.org/10.1016/j.ijantimicag.2011.01.011 PMid:21397461
Huang YT, Liao CH, Teng LJ, Hsueh PR. Comparative bactericidal activities of daptomycin, glycopeptides, linezolid and tigecycline against blood isolates of Gram-positive bacteria in Taiwan, Clin Microbiol Infect 2008;14(2):124-9. http://dx.doi.org/10.1111/j.1469-0691.2007.01888.x PMid:18076671
Lefebvre M, Jacqueline C, Amador G et al. Efficacy of daptomycin combined with rifampicin for the treatment of experimental methicillin-resistant Staphylococcus aureus (MRSA) acute osteomyelitis, Int J Antimicrob Agents 2010;36(6):542-4. http://dx.doi.org/10.1016/j.ijantimicag.2010.07.008 PMid:20851576
Mangili A, Bica I, Snydman DR, Hamer DH. Daptomycin-resistant, methicillin-resistant Staphylococcus aureus bacteremia, Clin Infect Dis 2005;40(7):1058-60. http://dx.doi.org/10.1086/428616 PMid:15825002
Öksüz L, Gürler N. Klinik örneklerden izole edilen metisiline dirençli stafilokok suşlarının son yıllarda kullanıma giren antibiyotiklere in- vitro duyarlılık sonuçları, ANKEM Derg 2009;23(2):71- 7.
Özaras R, Tabak F. Daptomisin, Klimik Dergisi 2010;23(2):35-8.
Petersen PJ, Bradford PA, Weiss WJ, Murphy TM, Sum PE, Projan SJ. In vitro and in vivo activities of tigecycline (GAR-936), daptomycin, and compara- tive antimicrobial agents against glycopeptide- intermediate Staphylococcus aureus and other resistant Gram-positive pathogens, Antimicrob Agents Chemother 2002;46(8):2595-601. http://dx.doi.org/10.1128/AAC.46.8.2595-2601.2002 PMid:12121938 PMCid:127327
Raad I, Hanna H, Jiang Y et al. Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm, Antimicrob Agents Chemother 2007;51(5): 1656-60. http://dx.doi.org/10.1128/AAC.00350-06 PMid:17353249 PMCid:1855569
Rehm SJ, Boucher H, Levine D et al. Daptomycin versus vancomycin plus gentamicin for treatment of bacteremia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates, J Antimicrob Chemother 2008;62(6):1413-21. http://dx.doi.org/10.1093/jac/dkn372 PMid:18782781 PMCid:2583068
Rybak MJ, Hershberger E, Moldovan T, Grucz RG. In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin against staphylococci and enterococci, including vancomycin- intermediate and -resistant strains, Antimicrob Agents Chemother 2000;44(4):1062-6. http://dx.doi.org/10.1128/AAC.44.4.1062-1066.2000 PMid:10722513 PMCid:89814
Sancak B. Staphylococcus aureus ve antibiyotik direnci, Mikrobiyol Bul 2011;45(3):565-76. PMid:21935792
Sorlozano A, Gutierrez J, Roman J, Liebana J, Piedrola G. Activity of daptomycin against multiresistant clinical isolates of Staphylococcus aureus and Streptococcus agalactiae, Microb Drug Resist 2009;15(2):1-3. http://dx.doi.org/10.1089/mdr.2009.0899 PMid:19432525
Tabak F. 2010da daptomisin, ANKEM Derg 2010;24(Ek 2):110-3.
Traczewski MM, Katz BD, Steenbergen JN, Brown SD. Inhibitory and bactericidal activities of daptomycin, vancomycin, and teicoplanin against methicillin-resistant Staphylococcus aureus isolates collected from 1985 to 2007, Antimicrob Agents Chemother 2009;53(5):1735-8. http://dx.doi.org/10.1128/AAC.01022-08 PMid:19223623 PMCid:2681544
Ulusoy S. Dirençli Gram pozitif kok infeksiyonlarında antimikrobiyal tedavi, ANKEM Derg 2001; 15(3):407-15.