Mustafa GÜZEL, Penka MONCHEVA, Petya HRISTOVA, Yasemin GENÇ, Altan AKSOY

Karbapenemlere dirençli non-fermenter Gram negatif basillerde antibiyotik direnci ve metallo-beta-laktamaz pozitifliği

Amaç: Gram negatif bakterilerde görülen antibiyotik direnci tüm dünyada giderek artan bir sorundur ve hem hastane içi hem de toplum kökenli enfeksiyonlarda hekimleri zorlayan bir konudur. Metallo-beta-laktamaz (MBL) üreten bakteriler ile oluşan enfeksiyonlar özellikle endişe vericidir; çünkü bu bakterilerdeki direnç genleri bir sınıf antibiyotiğin tümünü etkisiz kılabilirler. Ayrıca, MBL üreten bakteriler arasında çoklu ilaç dirençli suşların oranı da yüksek olmaktadır. Çoklu ilaç direnci non-fermenter Gram negatif basiller (NFGNB) arasında giderek artış göstermektedir. Bu çalışmada, hasta örneklerinden izole edilen karbapenem dirençli NFGNB (non-fermenter Gram negatif basiller)'de diğer antibiyotiklere direnç oranlarının ve E-test yöntemi ile MBL üretiminin araştırılması amaçlanmıştır.Yöntem: Ankara Numune Eğitim ve Araştırma Hastanesi Tıbbi Mikrobiyoloji Laboratuvarına Ocak 2014 ve Mart 2015 yılları arasında gönderilen yatan hasta örneklerinden izole edilen karbapenem dirençli NFGNB çalışmaya dahil edilmiştir. İmipenem ve/veya meropenem dirençli suşlar karbapenem dirençli olarak kabul edilmiştir. Fenotipik olarak MBL tayini için meropenem/meropenem+EDTA E-test stripleri kullanılmıştır.Bulgular: Çalışmaya 110 karbapenem dirençli NFGNB suş dahil edilmiştir. Bunların %44,5'i Acinetobacter baumannii, %36,4'ü Pseudomonas aeruginosa'dır. NFGNB suşlarının en fazla izole edildiği örnek trakeal aspirat (%37,9) olup bunu %22,3 ile kan, %17,5 ile yara ve %13,6 ile idrar örneği izlemiştir. Karbapenem dirençli tüm NFGNB Antibiotic resistance in Gram negative bacteria is an increasing problem worldwide and a challenging issue for the physicians in both nosocomial and community-acquired infections. The resistance problem has gained more importance along with the occurrence of antibiotic-degrading enzymes such as extended-spectrum beta-lactamases (ESBLs), carbapenemases (KPCs), and metallo-beta-lactamases (MBLs) among Enterobacteriaceae, Pseudomonas and Acinetobacter species (1). Infections caused by MBL-producing bacteria are particularly threatening as these resistance genes are usually located in transferable plasmids and may render an entire antibiotic class ineffective (2). Besides, the rates of multidrug- and pandrug-resistant strains are higher among MBL-producing bacteria (3).Multidrug resistance has been gradually increasing among non-fermentative Gram negative bacilli (NFGNB). Treatment of infections caused by bacteria resistant to the primary therapeutic agents such as beta-lactam, fluoroquinolone, aminoglycoside, and carbapenem group antibiotics is difficult and leads to a high cost (4). The present study aimed to investigate resistance rates of carbapenem resistant NFGNB isolated from patients' specimens to other antibiotics and to evaluate MBL production by E-test method.suşları göz önüne alındığında, en yüksek direnç oranları sırasıyla ampisilin-sulbaktam (%95,5), siprofloksasin (%87,8) ve sefepim (%83,3) için gözlenmiştir. MBL pozitifliği 110 suştan yalnızca birinde (%0,9) saptanmıştır. Bu suş idrar örneğinden izole edilen bir A. baumannii'dır. Sonuç: Giderek artan ve tedavisi güç ve maliyetli olan dirençli NFGNB enfeksiyonlarının kontrolünde klinik izolatların uygun antibiyogramı ve rutin MBL taraması ile enzim üreten suşların saptanması, sürveyansı ve akılcı antibiyotik kullanımı esastır.

Antibiotic resistance and metallo-beta-lactamase positivity in carbapenem-resistant non-fermentative Gram negative bacilli

Objective: Antibiotic resistance in Gram negativebacteria is an increasing problem worldwide and achallenging issue for the physicians in both nosocomialand community-acquired infections. Infections causedby metallo-beta-lactamase (MBL)-producing bacteriaare particularly threatening as the resistance genes ofthese bacteria may render an entire antibiotic classineffective. Moreover, the rates of multidrug-resistantstrains are also higher among MBL-producing bacteria.Multidrug resistance has been gradually increasingamong non-fermentative Gram-negative bacilli (NFGNB).The present study aimed to investigate resistance ratesof carbapenem-resistant NFGNB isolated from patients'specimens to other antibiotics and to evaluate MBLproduction by E-test method.Method: Carbapenem-resistant NFGNB, which wereisolated from the inpatients' specimens sent from January2014 through March 2015 to Ankara Numune Trainingand Research Hospital Medical Microbiology Laboratory,were included. Imipenem- and/or meropenem-resistantstrains were considered as carbapenem-resistant.Meropenem/meropenem+EDTA E-test strips were usedfor phenotypic MBL detection.Results: The study included 110 carbapenemresistantNFGNB strains. Of these strains, 44.5% wereAcinetobacter baumannii and 36.4% were Pseudomonasaeruginosa. The NFGNB strains were mostly isolated fromtracheal aspirate (37.9%), followed by blood (22.3%),wound (17.5%), and urine (13.6%) specimens. When allcarbapenem-resistant NFGNB strains were considered,the highest rate of resistance was ampicillin-sulbactam (95.5%), followed by ciprofloxacin (87.8%), and cefepime(83.3%). Of 110 strains, only 1 (0.9%) was determined tobe MBL positive. This was an Acinetobacter baumanniiisolated from urine sample.Conclusion: Detection of enzyme-producing strainsby appropriate antibiogram and routine MBL screeningof clinical isolates, surveillance, and rational antibioticuse are essential in the control of resistant NFGNBinfections, the rate of which is gradually increasing andthe treatment of which is difficult and costly.

PDF

___

1. Curcio D. Multidrug resistant Gram negative bacterial infections: are you ready for the challenge? Curr Clin Pharmacol, 2014; 9 (1): 27-38.
2. Fast W, Sutton LD. Metallo-?-lactamase: inhibitors and reporter substrates. Biochim Biophys Acta, 2013; 1834 (8): 1648-59.
3. Ranjan S, Banashankari G, Babu PS. Comparison of epidemiological and antibiotic susceptibility pattern of metallo beta lactamase positive and metallo beta lactamase negative strains of Pseudomonas aeruginosa. J Lab Physicians, 2014; 6(2): 109-13.
4. McGowan JE Jr. Resistance in non fermenting Gram negative bacteria: multidrug resistance to the maximum. Am J Infect Control, 2006; 34 (5 Suppl 1): S29-37; discussion S64-73.
5. Bulut Y, Çağlar H. Gram negatif non-fermantatif bakterilerde metallo beta laktamaz enziminin farklı yöntemlerle gösterilmesi. FÜ Sağ Bil Tıp Derg, 2013; 27 (3): 135-40.
6. Farajzadeh Sheikh A, Rostami S, Jolodar A, Tabatabaiefar MA, Khorvash F, Saki A, et al. Detection of metallo beta lactamases among carbapenem resistant Pseudomonas aeruginosa. Jundishapur J Microbiol, 2014; 7 (11): e12289.
7. Peter S, Lacher A, Marschal M, Hölzl F, Buhl M, Autenrieth I, et al. Evaluation of phenotypic detection methods for metallo ? lactamases (MBLs) in clinical isolates of Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis, 2014; 33 (7): 1133-41.
8. Sánchez A, Gattarello S, Rello J. New treatment options for infections caused by multiresistant strains of Pseudomonas aeruginosa and other nonfermenting Gram negative bacilli. Semin Respir Crit Care Med, 2011; 32 (2): 151-8.
9. Szejbach A, Mikucka A, Bogiel T, Gospodarek E. Usefulness of phenotypic and genotypic methods for metallo beta lactamases detection in carbapenem resistant Acinetobacter baumannii strains. Med Sci Monit Basic Res, 2013; 19: 32-6.
10. Gupta V, Garg R, Garg S, Chander J, Attri AK. Coexistence of extended spectrum betalactamases, AmpC beta lactamases and metallobeta lactamases in Acinetobacter baumannii from burns patients: a report from a tertiary care centre of India. Ann Burns Fire Disasters, 2013; 26 (4): 189-92.
11. Bialvaei AZ, Samadi Kafil H. Colistin, mechanisms and prevalence of resistance. Curr Med Res Opin, 2015; 31 (4): 707-21.
12. Hsueh PR, Chen WH, Luh KT. Relationships between antimicrobial use and antimicrobial resistance in Gram negative bacteria causing nosocomial infections from 1991-2003 at a university hospital in Taiwan. Int J Antimicrob Agents, 2005; 26 (6): 463-72.
13. Lai CC, Wang CY, Chu CC, Tan CK, Lu CL, Lee YC, et al. Correlation between antibiotic consumption and resistance of Gram negative bacteria causing health care associated infections at a university hospital in Taiwan from 2000 to 2009. J Antimicrob Chemother, 2011; 66 (6): 1374-82.
14. Yan JJ, Wu JJ, Tsai SH, Chuang CL. Comparison of the double disk, combined disk, and E test methods for detecting metallo beta lactamases in Gram negative bacilli. Diagn Microbiol Infect Dis, 2004; 49 (1): 5-11.
15. Kaleem F, Usman J, Hassan A, Khan A. Frequency and susceptibility pattern of metallo beta lactamase producers in a hospital in Pakistan. J Infect Dev Ctries, 2010; 4 (12): 810-3.
16. Aksoy MD, Çavuşlu Ş, Tuğrul HM. Investigation of metallo beta lactamases and oxacilinases in carbapenem resistant Acinetobacter baumannii strains isolated from inpatients. Balkan Med J, 2015; 32 (1): 79-83.
17. Vasoo S, Barreto JN, Tosh PK. Emerging Issues in Gram negative bacterial resistance: An update for the practicing clinician. Mayo Clin Proc, 2015; 90 (3): 395-403.
18. Abdallah M, Olafisoye O, Cortes C, Urban C, Charles C, Landman D, et al. Reduction in the prevalence of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in New York City. Am J Infect Control, 2015; pii: S0196-6553(15) 00114-5.