İlkay KARAOĞLAN, Yasemin ZER, Aynur SÜNER, Mustafa NAMIDURU

Bazı Enterobacteriaceae türlerine ertapenemin in-vitro etkinliği

Yeni bir karbapenem grubu antibiyotik olan ertapenemin Escherichia coli, Klebsiella pneumoniae ve Proteus spp. suşlarına in-vitro etkinliği belirlenmiştir. Bakterilerin tanımlanması klasik yöntemler ve Vitek2 tam otomatik bakteri tanımlama sistemi ile, antibiyotik duyarlılıkları disk difüzyon yöntemi ile, GSBL enzimi de çift disk sinerji yöntemi ile araştırılmıştır. Çalışma 81’i (% 62) E.coli, 39’u (% 30) K.pneumoniae ve 10’u (% 8) Proteus spp. olarak tanımlanan toplam 130 suş ile yapılmıştır. Bakterilerden 98’i (% 75) yatan hastalardan, 32’si (% 25) poliklinik takibinde olan hastalardan izole edilmiştir. Suşlarda karbapenemler dışındaki antibiyotiklere yüksek direnç oranları tespit edilmiştir. Yatan hastalardan izole edilen 60 E.coli suşunun 40’ında (% 67), 33 K.pneumoniae suşunun 19’unda (% 58); poliklinik hastalarından izole edilen 21 E.coli suşunun 9’unda (% 43) ve 6 Klebsiella suşunun 2’sinde (% 33) GSBL pozitifliği saptanmıştır. İzole edilen 10 Proteus spp. suşunda GSBL pozitifliğine rastlanmamıştır. GSBL pozitif K.pneumoniae suşlarından 1’i ve GSBL pozitif E.coli suşlarından 1’i imipeneme dirençli olarak bulunmuştur. İmipenem direnci bulunan suşlar ertapeneme de dirençli olarak saptanmıştır. Ayrıca GSBL pozitif, imipeneme duyarlı 2 E.coli suşu da ertapeneme dirençli bulunmuş, böylece hepsi GSBL pozitif 4 suşta (% 3) ertapenem direncine rastlanmıştır. Ertapenem in-vitro olarak E.coli ve K.pneumoniae suşlarına yüksek oranda etkili bulunmuş, bu bakteriler ile oluşan infeksiyonların tedavisinde iyi bir alternatif olabileceğini düşünülmüştür.

Anahtar Kelimeler:

beta-Laktamazlar, Enterobacteriaceae, In vitro, Klebsiella pneumoniae

In-vitro activity of ertapenem to some Enterobacteriaceae species

The aim of this paper is to determine the in-vitro activity of ertapenem, a new carbapenem, for Escherichia coli, Klebsiella pneumoniae and Proteus spp. isolates. The bacteria were identified by Vitek2 microbial identification system and conventional methods, antimicrobial susceptibility tests were performed by disk diffusion method according to CLSI and isolates were examined for ESBL by double disk synergy test. Of 130 clinical isolates, 81 were E.coli (62 %), 39 were K.pneumoniae (30 %) and 10 were Proteus spp. (8 %). Of these strains, 98 (75 %) were isolated from hospitalized patients and 32 (25 %) from outpatients. High resistance rates were found for all antibiotics except carbapenems. Forty (67 %) of 60 E.coli strains, 19 (58 %) of 33 K.pneumoniae strains isolated from hospitilazed patients and 9 (43 %) of 21 E.coli strains, 2 (33 %) of 6 K.pneumoniae strains isolated from outpatients were detected as ESBL producers. None of 10 Proteus spp. strains produced ESBL. Imipenem resistance was detected in 1 E.coli and 1 K.pneumoniae strains, both of which were ESBL positive. These two imipenem resistant isolates were also ertapenem resistant. In addition, 2 other ESBL positive E.coli isolates were also found resistant to ertapenem; so as a total, 4 ESBL positive isolates (3 %) were resistant to ertapenem. Ertapenem demonstrated in-vitro potent activity against E.coli and K.pneumoniae. Ertapenem may be a good alternative for the therapy of infections due to ESBL producing E.coli and K.pneumoniae starins.

Keywords:

beta-Lactamases, Enterobacteriaceae, In Vitro, Klebsiella pneumoniae,

PDF

___

1. Akova M: Dikkat: Genişlemiş spektrumlu betalaktamaz (GSBL) var! ANKEM Derg 2004;18(Ek2):98-103.
2. Aldridge KE: Ertapenem (MK-0826), a new karbapenem: comparative in vitro activity against clinically significant anaerobes, Diagn Microbiol Infect Dis 2002;44(2):181-6.
3. Azap Kurt Ö, Timurkaynak F, Yapar G, Çağır Ü, Arslan H: Genişlemiş spektrumlu beta-laktamaz salgılayan ve salgılamayan Escherichia coli, Klebsiella suşlarında ko-trimoksazol, sefepim ve karbapenem duyarlılıkları, Hastane İnfeksiyon Derg 2006;10(3):191-5.
4. Betriu C, Salso S, Sancez A et al: Comparative in vitro activity and the inoculum effect of ertapenem against Enterobactericeae resistant to extended-spectrum cephalosporins, Int J Antimicrob Agents 2006;28(1):1-5.
5. Bradford P: Extended-spectrum beta-lactamases in the 21st century: Characterization, epidemiology, and detection of this important threat, Clin Microbiol Rev 2001;14(4):933-51.
6. Bush K, Miller GH: Bactericidal enzymatic resistance: beta-lactamases and aminoglycosidemodifying enzymes, Curr Opin Microbiol 1998;1(5):509-55.
7. Centers for Disease Control and Prevention (CDC): National Nosocoial Infections Surveillance System (NNIS). Antimicrobial resistance ICU surveillance report (www.cdc.gov/ncidod/dhqp/pdf/ nnis/2004NNISreport.pdf).
8. Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility Testing; Eighteenth Informational Supplement, M100-S18, CLSI, Wayne (2008).
9. Dos Santos KV, Diniz CG, Cautinho SC et al: In vitro activity of piperacillin/tazobactam and ertapenem against Bacteroides fragilis and Escherichia coli in pure and mixed culture, J Med Microbiol 2007;56(Pt 6):798-802.
10. Gülay Z: Gram negatif basillerde antibiyotik direnci: 2003-2005 yılında ülkemizdeki durum, “Gür D, Köksal İ, Başustaoğlu AC, Gülay Z (eds): 7. Antimikrobik Kemoterapi Günleri, Program ve Özet Kitabı”, s.161-76, Türk Mikrobiyoloji Cemiyeti Yayını No.54, İstanbul (2006).
11. Gür D: Toplumdan kazanılmış infekiyonlarda betalaktamazların rolü, ANKEM Derg 2006;20(Ek 2):274-7.
12. Kiremitçi A, Dinleyici EC, Erben N et al: In vitro activity of ertapenem and other carbapenems against extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae clinical isolates in a tertiary care center in Turkey, Expert Opin Pharmacother 2008;9(9):1441-9.
13. Kohler J, Dorso KL, Young K et al: In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum betalactamase and extended-spectrum beta-lactamaseproducing Klebsiella pneumoniae and Escherichia coli clinical isolates, Antimicrob Agents Chemother 1999;43(5):1170-6.
14. Leblebicioglu H, Rosenthal VD, Arıkan ÖA et al: Device-associated hospital-acquired infection rates in Turkish intensive care units. Findings of the International Nosocomial Infection Control Consortium (INICC), J Hosp Infect 2007;65(3):251-7.
15. Lipsky BA, Armstrong DG, Citron DM, Tice AD, Morgenstern DE, Abramson MA: Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP): prospective, randomised, controlled, double-blinded, multicenter trial, Lancet 2005;366(9498):1695-703.
16. Livermore DM, Oakton KJ, Carter MW, Warner M: Activity of ertapenem (MK-0826) versus Enterobactericeae with potent beta-lactamases, Antimicrob Agents Chemother 2001;45(10):2831-7.
17. Livenmore DM, Sefton AM, Scott GM: Properties and potential of ertapenem, J Antimicrob Chemother 2003;52(3):331-44.
18. Mody RM, Erwin DP, Summers AM et al: Ertapenem susceptibility of extended spectrum beta-lactamase-producing organisms, Ann Clin Microbiol Antimicrob 2007;6:1-6.
19. Paterson DL, Mulazimoglu L, Casellas JM et al: Epidemiology of ciprofloxacin resistance and its relationship to extended spectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremia, Clin Infect Dis 2000;30(3):473-8.
20. Paterson DL, Rossi F, Baquero F et al: In vitro susceptibilities of aerobic and facultative gram negative bacilli isolated from patients with intra-abdominal infections worldwide: the 2003 Study for Monitoring Antimicrob Resistance Trends (SMART), J Antimicrob Chemother 2005;55(6):965-73.
21. Raveh D, Yinnon AM, Broide E, Rudensky B: Susceptibilities of ESBL-producing Enterobactericeae to ertapenem, meropenem and piperacillintazobactam with and without clavulanic acid, Chemotherapy 2007;53(3):185-9.
22. Reese AM, Frei CR, Burgess DS: Pharmacodynamics of intermittent and continuous infusion piperacillin/ tazobactam and cefepime against extendedspectrum beta-lactamase-producing organisms, Int J Antimicrob Agents 2005;26(2):114-9.
23. Shah AA, Hasan F, Ahmed S, Hameed A: Extended spectrum beta-lactamases (ESBLs): characterization, epidemiology and detection, Crit Rev Microbiol 2004;30(1):25-32.
24. Shah PM, Isaacs RD: Ertapenem, the first of a new group of carbapenems, J Antimicrob Chemother 2003;52(4):538-42.
25. Solomkin J, Yelin AE, Rotstein OD et al: Ertapenem versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections: results of a double-blind, randomized comparative phase III trial, Ann Surg 2003;237(2):235-45.
26. The European Antimicrobial Resistance Surveilance System (EARSS): Annual report 2006(www.rivm.nl/earss).
27. Thomson KS, Sanders CC: Detection of extendedspectrum beta-lactamases in members of family Enterobacteriaceae: comparison of the double disk and three-dimersional tests, Antimicrob Agents Chemother 1992;36(9):1877-82.
28. Wexler HM: In vitro activity of ertapenem: review of recent studies, J Antimicrob Chemother 2004;53(Suppl 2):11-21.