Ampc beta-laktamazlar

Genişlemiş spekturumlu beta-laktamazlar (GSBL’ler) karbapenem ve sefamisinler hariç olmak üzere penisilin, oksiiminosefalosporin ve monobaktamlara direnç sağlamakta, ancak bu enzimlerin hidrolitik aktiviteleri genellikle klavulanik asitle inhibe olmaktadır. AmpC beta-laktamazlar ise karbapenem hariç olmak üzere daha geniş spektrumdaki beta-laktam antbiyotiklere direnç sağlamakta ve bu enzimlerin hidrolitik aktivitesi klavulanik asitle inhibe olmamaktadır. Sefamisin direnci AmpC beta-laktamazların varlığı hakkında fikir vermektedir ancak porin kaybı da bu durumu taklit edebilmektedir. AmpC beta- laktamazların tanısında kullanılan fenotipik ve moleküler yöntemler AmpC beta-laktamazlarla porin kaybını birbirinden ayırdetmektedirler. Fakat fenotipik yöntemlerin hiçbiri kromozomal kaynaklı AmpC beta-laktamaz ile plazmid kaynaklı AmpC beta-laktamazları ayırt edememektedir. AmpC beta-laktamaz tanısında kullanılan indirekt yöntemler; Üç boyutlu enzim ekstrakt test (3BT), Tris-EDTA’lı AmpC disk testi, sefoksitin agar besiyerinde üretme (CAM), modifiye Hodge testi ile spot inokülasyon testidir. AmpC enzim tayininde doğrulama testleri olarak önerilen inhibitör temelli direkt yöntemler; boronik asit (BA) inhibisyon disk testi, LN-2-128, Ro-48-1220 inhibisyon disk testi, Syn2190 inhibisyon disk testi, piperasilin ve piperasilin-tazobaktam inhibisyon disk testi, kloksasilin çift disk sinerji testi, E-test, izoelektrik odaklama metodu (İEO), multipleks PCR, konjugasyon deneyleri ve ELİZA test. Bu derleme yazıda yukarıda bahsedilen yöntemlerin performansları değerlendirilmiş ve indirekt ve direkt yöntemler kullanılarak AmpC+GSBL, sadece AmpC beta-laktamaz ve sadece GSBL tespit edilen çalışmalar özetlenmiştir.

AmpC beta-lactamases

Expanded-spectrum beta-lactamases (ESBL’s) can confer resistance to penicillins, oxiiminocephalosporins and monobactam but not carbapenems and cephamycin, and their hidrolytic activities are usually inhibited by clavulanic acid. AmpC beta-lactamases also confer resistance to expanded-spectrum beta-lactam antibiotics but not carbapenems, and their hidrolytic activities are poorly inhibited by clavulanic acid. Resistance to a cephamycin is suggestive of the presence an AmpC enzyme but this can be mimicked by porin loss. Phenotypic and molecular methods that used in detection of AmpC beta-lactamases distinguish between AmpC beta-lactamase and porin loss. But none of the phenotypic methods can distinguish between plasmid-borne-AmpC beta-lactamase and chromosome-borne AmpC beta-laktamase. Indirekt methods that used in detection of AmpC beta-lactamases are three dimensional extract test (3DET), AmpC disk test (impregnanted Tris-EDTA), cefoxitin agar medium (CAM), modified Hodge test and spot inoculation test. Direct methods (inhibitor based methods) that used in detection of AmpC beta-lactamases are boronic acid (BA), LN-2-128, Ro-48-1220, Syn2190, piperacilin and piperacilin- tazobactam inhibition test, cloxacillin double disk sinergic test, E-test, isoelectric focus method (IEF), multiplex PCR, conjugation test and ELISA test. In this paper the performances of these methods that mentioned above are evaluated and summarized investigations about detection of both AmpC and ESBL producers, only AmpC producers and only ESBL producers by using indirect and direct methods.

PDF

___

1.Ak S. Escherichia coli ve Klebsiella spp. klinik izolatlarında plazmid aracılı AmpC beta-laktamaz tespiti, Uzmanlık Tezi, Hacettepe Üniversitesi Tıp Fakültesi, Ankara (2008).
2.Alvarez M, Tran JH, Chow N, Jacoby GA. Epidemiology of conjugative plasmid-mediated AmpC beta-lactamases in the United States, Antimicrobial Agents Chemother 2004;48(2):533-7. PMid:17112770
3.Arora S, Bal M. AmpC beta-lactamase producing bacterial isolates from Kolkata Hospital, Indian J Med Res 2005;122(3):224-33. PMid:16910916
4.Babini GS, Danel F, Munro SD, Micklesen PA, Livermore DM. Unusual tazobactam sensitive AmpC beta-lactamase from two Escherichia coli isolates, J Antimicrob Chemother 1998;41(1):115-8.
5.Bauernfeind A, Stemplinger I, Jungwirth R, Giamarellou H. Characterization of the plasmidic beta-lactamase CMY-2, which is responsible for cephamycin resistance, Antimicrob Agent Che- mother 1996;40(1):221-4.
6.Black JA, Moland ES, Thomson KS. AmpC disc test for detection of plasmid-mediated AmpC beta-lactamases in Enterobacteriaceae lacking chromosomal AmpC beta-lactamases, J Clin Microbiol 2005;43(7):3110-3. PMid:15491323
7.Black JA, Thomson KS, Buynak JD, Pitout JD. Evaluation of beta-lactamase inhibitors in disk tests for detection of plasmid mediated AmpC beta-lactamases in well-characterized clinical strains of Klebsiella spp., J Clin Microbiol 2005; 43(8):4168-71. PMid:1432735
8.Black JA, Thomson KS, Pitout JD. Use of beta- lactamase inhibitors in disk tests to detect plasmid- mediated AmpC beta-lactamases, J Clin Microbiol 2004;42(5):2203-6.
9.Brenwald NP, Jevons G, Andrews J, Ang L, Fraise AP. Disc methods for detecting AmpC beta- lactamases producing clinical isolates of Escherichia coli and Klebsiella pneumoniae, J Antimicrob Chemother 2005;56(3):600-1. PMid:11712782
10.Coşkun S. Escherichia coli ve Klebsiella pneumoniae klinik izolatlarında plazmid aracılı AmpC beta-laktamaz tespiti, Doktora tezi, A.Ü. Eczacılık Fakültesi Farmasötik Mikrobiyoloji Anabilim Dalı, Ankara (2011). PMid:9176791
11.Coudron PE. Inhibitor based methods for detection of plasmid mediated AmpC beta-lactamases in Klebsiella spp., Escherichia coli and Proteus mirabilis, J Clin Microbiol 2005;43(8):4163-7. PMid:10972347
12.Coudron PE, Hanson ND, Climo MW. Occurence of extended-spectrum and AmpC beta-lactamases in bloodstream isolates of Klebsiella pneumoniae: isolates harbor plasmid-mediated FOX-5 and ACT-1 AmpC beta-lactamases, J Clin Microbiol 2003;41(2):772-7. PMid:11695759
13.Coudron PE, Moland ES, Thomson KS. Occurrence and detection of AmpC beta-lactamases among Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis isolates at a veterans medical center, J Clin Microbiol 2000;38(5):1791-6.
14.Demirbakan H, Midilli K, Öğünç D et al. Sefoksitine dirençli ya da az duyarlı saptanan Klebsiella spp. ve Escherichia coli izolatlarında plazmid aracılı AmpC beta-laktamaz enzim tiplerinin araştırılması, Mikrobiyol Bul 2008;42(4):545-51. PMid:16137496
15.Ding H, Yang Y, Lu Q et al. The prevalence of plasmid mediated AmpC beta-lactamases among clinical isolates of Escherichia coli and Klebsiella pneumoniae from five childrens hospitals in China, Eur J Clin Microbiol Infect Dis 2008; 27(10):915-21. PMid:16914114
16.Doi Y, Shibata N, Shibayama K et al. Characte- rization of a novel plasmid mediated cephalosporinase (CMY-9) and its genetic environment in an Escherichia coli clinical isolate, Antimicrob Agents Chemother 2002;46(8):2427-34.
17.Doi Y, Paterson DL. Detection of plasmid-mediated class C beta-lactamases, Int J Infect Dis 2007;11(3): 191-7. PMid:12076323
18.Gür D. Beta-laktamazlar, Hacettepe Tıp Derg 2002; 33(2):102-9. PMid:17826304
19.Empel J, Baraniak A, Literacka E et al. Molecular survey of beta-lactamases conferring resistance to newer beta-lactams in Enterobacteriaceae isolates from Polish hospitals, Antimicrob Agents Che- mother 2008;52(7):2449-54. PMid:15772596
20.Eroğlu Ö, Cömert FB, Külah C, Aktaş E. Genişlemiş spektrumlu beta-laktamazlar (GSBL) üreten Klebsiella pneumoniae ve Klebsiella oxytoca kökenlerinde enzim tiplerinin izoelektrik odaklama yöntemi ile belirlenmesi, Türk Mikrobiyol Cem Derg 2007;37(2):76-84. PMid:11271627
21.Ingram PR, Inglis TJ, Vanzetti TR, Henderson BA, Harnett GB, Murray RJ. Comparison of methods for AmpC beta-lactamase detection in Entero- bacteriaceae, J Med Microbiol 2011;60(Pt 6):715-21. PMid:1381431
22.Jacoby GA, Walsh KE, Walker VJ. Identification of extended spectrum, AmpC and carbapenem- hydrolyzing beta-lactamases in Escherichia coli and Klebsiella pneumoniae by disk tests, J Clin Microbiol 2006;44(6):1971-6.
23.Jacoby GA. AmpC beta-lactamases, Clin Microbiol Rev 2009;22(1):161-82. PMid:12581382
24.Jeong SH, Song W, Kim JS, Kim HS, Lee KM. Broth microdilusyon method to detect extended spectrum beta-lactamases and AmpC-type beta-lactamase in Enterobacteriaceae isolates by use of clavulanic acid and boronic acid as inhibitors, J Clin Microbiol 2009;47(11):3409-12.
25.Koldaş K. Gram negatif bakterilerde plazmid aracılı AmpC beta-laktamaz tespiti, Uzmanlık Tezi, Ankara Numune Eğitim ve Araştırma Hastanesi, Ankara (2009).
26.Lee K, Hong SG, Park YJ et al. Evaluation of phe-notypic screening methods for detecting plasmid- mediated AmpC beta-lactamases-producing iso - lates of Escherichia coli and Klebsiella pneumoni -ae, Diagn Microbiol Infect Dis 2005;53(4):319-23.
27.Lee K, Lee M, Shin JH et al. Prevalence of plasmid- mediated AmpC beta-lactamases in Escherichia coli and Klebsiella pneumoniae in Korea, Microb Drug Resist 2006;12(1):44-9. PMid:8183579
28.Li Y, Li Q, Du Y et al. Prevalence of plasmid- mediated AmpC beta-lactamases in a Chinese University Hospital from 2003 to 2005: First report of CMY-2 type AmpC beta-lactamase resistance in China, J Clin Microbiol 2008;46(4):1317-21. PMid:16475695
29.Mirelis B, Riveara A, Miró E, Mesa RJ, Navarro F, Coll P. A simple phenotipic method for differentiation between acquired and chromosomal AmpC beta-lactamases in Escherichia coli, Enferm Infec Microbiol Clin 2006;24(6):370-2. PMid:17608758
30.Moland ES, Black JA, Ourada J, Reisbig MD, Hanson ND, Thomson KS. Occurence of newer beta-lactamases in Klebsiella pneumoniae isolates from 24 US hospitals, Antimicrob Agents Chemother 2002;46(12):3837-42.
31.Moland ES, Hanson ND, Black JA, Hossain A, Song W, Thomson KS. Prevalence of newer beta- lactamases in gram-negative clinical isolates collected in the United States from 2001 to 2002, J Clin Microbiol 2006;44(9):3318-24.
32.Nasim K, Elsayed S, Pitout JD, Conly J, Churc DL, Gregson DB. New method for laboratory detection of AmpC beta-lactamases in Escherichia coli and Klebsiella pneumoniae, J Clin Microbiol 2004;42(10):4799-802.
33.Pai H, Kang CI, Byeon JH et al. Epidemiology and clinical features of bloodstream infections caused by AmpC type beta-lactamase-producing Kleb- siella pneumoniae. Antimicrob Agent Chemother 2004;48(10):3720-8.
34.Park SD, Uh Y, Lee G, Lim K, Kim JB, Jeong SH. Prevalence and resistance patterns of extended spectrum and AmpC beta-lactamase in Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Salmonella serovar Stanley in a Korean tertiary hospital, APMIS 2010;118(10):801-8.
35.Perez-Perez FJ, Hanson ND. Detection of plasmid- mediated AmpC beta-lactamase genes in clinical isolates by using multiplex PCR, J Clin Microbiol 2002;40(6):2153-62.
36.Pitout JD, Gregson DB, Church DL, Laupland KB. Population based laboratory surveillance for AmpC beta-lactamase-producing Escherichia coli, Calgary, Emerg Infect Dis 2007;13(3):443-8.
37.Reisbig MD, Hossain A, Hanson ND. Factors influencing gene expression and resistance for gram - negative organisms expressing plasmid - encoded AmpC genes of Enterobacter origin, J Antimicrob Chemother 2003;51(5):1141-51.
38.Robberts FJ, Kohner PC, Patel R. Unreliable extended-spectrum beta-lactamase detection in the presence of plasmid-mediated AmpC in Escherichia coli clinical isolates, J Clin Microbiol 2009;47(2):358-61.
39.Shahid M, Malik A, Agrawal M, Singhal S. Phenotypic detection of extended-spectrum and AmpC beta-lactamases by a new spot-inoculation method and modified three-dimensional extract test: comparison with the conventional three- dimensional extract test, J Antimicrob Chemother 2004;54(3):684-7.
40.Sidjabat HE, Paterson DL, Qureshi ZA et al. Clinical features and molecular epidemiology of CMY-type beta-lactamase producing Escherichia coli, Clin Infect Dis 2009;48(6):739-44.
41.Song W, Jeong SH, Kim JS et al. Use of boronic acid disk methods to detect the combined expression of plasmid-mediated AmpC beta-lactamases and extended-spectrum beta-lactamases in clinical isolates of Klebsiella spp., Salmonella spp., and Proteus mirabilis, Diagn Microbiol Infect Dis 2007; 57(3):315-8.
42.Taneja N, Rao P, Arora J, Dogra A. Occurence of ESBL and AmpC beta-lactamases and susceptibi - lity to newer antimicrobial agents in complicated UTI, Indian J Med Res 2008;127(1):85-8.
43.Tenover FC, Emery SL, Spiegel CA et al. Identification of plasmid-mediated AmpC beta- lactamases in Escherichia coli, Klebsiella spp., and Proteus species can potentially improve reporting of cephalosporin susceptibility testing results, J Clin Microbiol 2009;47(2):294-9.
44.Tsakris A, Poulou A, Themeli-Digalaki K et al. Use of boronic acid disk tests to detect extended spectrum beta-lactamases in clinical isolates of KPC carbapenemase possessing Enterobacteriaceae, J Clin Microbiol 2009;47(11):3420-6.
45.UK National Guidelines for Laboratories. Detection and characterisation of beta-lactamase resistance in Gram negative bacteria of veterinary significance. Issued by the Veterinary and Public Health Test Standardisation Group A Subgroup of the UK Surveillance Group for Disease and Infections of Animals (SGDIA) 2005.
46.Wang QT, Liu YM, Wang H, Sun HL, Chen MJ, Du XL. Plasmid mediated cephalosporinase among extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae, Zhoghua Nei Ke Za Zhi 2004;43(7):487-90.
47.Winokur PL, Brueggemann A, DeSalvo DL et al. Animal and human multidrug-resistant, cepha losporin-resistant Salmonella isolates expressing a plasmid-mediated CMY-2 AmpC beta-lactamase, Antimicrob Agent Chemother 2000; 44(10):2777-83.
48.Yagi T, Wachino J, Kurokawa H et al. Practical methods using boronic asid compounds for identification of class C beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli, J Clin Microbiol 2005;43(6):2551-8.
49.Yan JJ, Hsueh PR, Lu JJ et al. Extended-spectrum beta-lactamases and plasmid-mediated AmpC enzymes among clinical isolates of Escherichia coli and Klebsiella pneumoniae from seven medical centers in Taiwan, Antimicrob Agent Chemother 2006;50(5):1861-4.
50.Yiğit H, Queenan AM, Anderson GJ et al. Novel carbapenem-hidrolyzing beta-lactamases KPC-1 from a carbapenem-resistant strain of Klebsiella pneumoniae, Antimicrob Agent Chemother 2001; 45(4):1151-61.