Rahmet GÜNER, Tümer GÜVEN, Zeliha TUFAN KOÇAK, Gül Ruhsar YILMAZ, Ziya Cibali AÇIKGÖZ, Mehmet Akın TAŞYARAN, Fatma ESER

Karbapenem Dirençli Enterobacteriacae Enfeksiyonları: Risk Faktörleri

Amaç: Enterobacteriaceae ailesi ve özellikle Klebsiella pneumoniae tedavisi zor ve artan direnç durumu ile birlikte tedavi seçenekleri daha da sınırlı hale gelen enfeksiyon etkenleridir. Çalışmamızda karbapenem dirençli Enterobacteriaceae KDE ile enfekte olan hastaların demografik özelliklerinin ve enfeksiyon risk faktörlerinin belirlenmesi amaçlanmıştır. Gereç ve Yöntemler: Ocak 2010 – Nisan 2014 tarihleri arasında hastanemizde KDE’nin etken olduğu enfeksiyon tanısı alan 25 hasta olgu grubu olarak çalışmaya dahil edildi. Olgu grubu hastalar ile aynı dönemde ve aynı klinikte yatan toplam 71 hasta kontrol grubu olarak belirlendi. Her iki grup için de hastaların demografik özellikleri ve sağlık bakımı ilişkili karakteristikleri değerlendirildi.Bulgular: Hastaların 20 %80 ’sinde K. pneumoniae, 2 %8 ’sinde Escherichia coli, 2 %8 ’sinde Enterobacter cloaca, 1 %4 ’inde Enterobacter aerogenes izole edildi. Tek değişkenli analizde SAPS II, YBÜ’de yatış öyküsü ve son 3 ayda antibiyotik kullanımı anlamlı risk faktörleri olarak bulundu p≤0,05 . Lojistik regresyon analizinde SAPS II OR 0,95; %95 GA 0,90-0,99, p=0,03 , YBÜ’de yatış öyküsü OR 8,5; %95 GA 2,25-32,51, p=0,04 ve son 3 ayda antibiyotik kullanımı OR 0,01; %95 GA 1,3-1,7, p=0,01 kolistin dirençli mikroorganizma enfeksiyonu için risk faktörü olma açısından bağımsız değişkenler olarak saptandı. On üç hastanın tedavisinde monoterapi, 10 hastanın tedavisinde kombine antibiyotik tedavisi kullanıldı. KDE izolatlarının en duyarlı olduğu antibiyotik grubu aminoglikozidler olarak tespit edildi.Sonuç: KDE’nin neden olduğu enfeksiyonlar artmış morbidite ve mortalite ile ilişkili olmaları ve sınırlı tedavi alternatifleri nedeni ile sıkı kontrol önlemleri alınması gereken bir sağlık bakım sorunudur. Bu amaçla, daha çok sayıda hastayı içeren çalışmalar ile risk faktörlerinin irdelenmesi gerekmektedir

Anahtar Kelimeler:

Karbapenem, Direnç, Enterobacteriaceae, K. pneumoniae, Risk faktörleri

Carbapenem-resistant Enterobacteriaceae Infections: Risk Factors

Objective: Increasing antibiotic resistance has become an important problem for the Enterobacteriaceae family and particularly for Klebsiella pneumonia. The aim of this study was to determine the demographic features of patients with carbapenem-resistant Enterobacteriaceae CRE infections and the relevant risk factors.Material and Methods: A total of 25 patients were included between January 2010 and April 2014 in the study as the case group infected with CRE. For the control group, 71 patients were chosen from the same clinics and concurrently hospitalised patients. All the patients’ demographic features and health care associated characteristics were evaluated in terms of possible risk factors.Results: Twenty 80% of the isolates were K. pneumoniae, 2 8% Esherichia coli, 2 8% Enterobacter cloaca, and 1 4% Enterobacter aerogenes. On univariate analysis, a high SAPS II score, history of ICU admissions, and antibiotic use within the last 3 months were found to be risk factors p≤0.05 . Logistic regression analysis revealed that the SAPS II score OR 0.95;CI 0.90-0.99,p=0.03 , history of ICU admissions OR 8.5;CI 2.25-32.51,p=0.04 and antibiotic use within the last 3 months OR 0.01;CI 1.3-1.7,p=0.01 were independent risk factors for CRE infection. Monotherapy was used for 13 patients and combination therapy for 10 patients. Aminoglycosides were the antibiotic group the CRE isolates were most commonly sensitive to.Conclusion: CRE infections are associated with increased morbidity and mortality. Treatment alternatives for these infections are limited and strict precautions are needed for this health care problem. The risk factors should therefore be evaluated with studies including more patients

Keywords:

Carbapenem, Resistance, Enterobacteriaceae, K. pneumoniae, Risk factor,

PDF

___

Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008;29:1099–106.
Hussein K, Raz-Pasteur A, Finkelstein R, Neuberger A, Shachor-Meyouhas Y, Oren I, Kassis I. Impact of carbapenem resistance on the outcome of patients’ hospital-acquired bacteraemia caused by Klebsiella pneumoniae. J Hosp Infect 2013;83 (4):307-13.
Dizbay M, Tunccan OG, Karasahin O, Aktas F. Emergence of carbapenem resistant Klebsiella spp. infections in a Turkish university hospital: Epidemiology and risk factors J Infect Dev Ctries 2014; 8 (1):44-9.
Facility Guidance for Control of Carbapenem Resistant Enterobacteriaceae (CRE) November 2015 Update. http://www.cdc.gov/hai/organisms/cre/cre-toolkit/
Sanchez GV, Master RN, Clark RB, Fyyaz M, Duvvuri P, Ekta G, Bordon J. Klebsiella pneumoniae antimicrobial drug resistance, United States, 1998-2013. Emerg Infect Dis 2013;19 (1):133-6.
Curiao T, Morosini MI, Ruiz-Garbajosa P, Robustillo A, Baquero F, Coque TM, Cantón R. Emergence of bla KPC-3-Tn4401a associated with a pKPN3/4-like plasmid within ST384 and ST388 Klebsiella pneumoniae clones in Spain. J Antimicrob Chemother 2010;65 (8):1608-14.
Mendes RE1, Mendoza M, Banga Singh KK, Castanheira M, Bell JM, Turnidge JD, Lin SS, Jones RN. Regional resistance surveillance program results for 12 Asia-Pacific nations (2011). Antimicrob Agents Chemother 2013;57 (11):5721-6.
Leblebicioglu H, Cakir N, Celen M, Kurt H, Baris H, Laeuffer J. Comparative activity of carbapenem testing (the COMPACT study) in Turkey. BMC Infect Dis 2012;12:42.
Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S, Schwartz D, Leavitt A, Carmeli Y. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother 2008; 52:1028-33.
Hussein K, Sprecher H, Mashiach T, Oren I, Kassis I, Finkelstein R. Carbapenem resistance among Klebsiella pneumoniae isolates: Risk factors, molecular characteristics, and susceptibility patterns. Infect Control Hosp Epidemiol 2009; 30:666-71.
Wiener-Well Y, Rudensky B, Yinnon AM, Kopuit P, Schlesinger Y, Broide E, Lachish T, Raveh D. Carriage rate of carbapenem resistant Klebsiella pneumoniae in hospitalised patients during a national outbreak. J Hosp Infect 2010; 74:344-9.
Daikos GL, Petrikkos P, Psichogiou M, Kosmidis C, Vryonis E, Skoutelis A, Georgousi K, Tzouvelekis LS, Tassios PT, Bamia C, Petrikkos G. Prospective observational study of the impact of VIM-1 metallo-beta- lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother 2009; 53:1868-73.
Lee GC, Burgess DS. Treatment of Klebsiella pneumoniae carbapenemase (KPC) infections: a review of published case series and case reports. Ann Clin Microbiol Antimicrob 2012; 13:11:32.
Falagas ME, Lourida P, Poulikakos P, Rafailidis PI, Tansarli GS. Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: Systematic evaluation of the available evidence. Antimicrob Agents Chemother 2014;58(2):654-63.
Clinical and Laboratuary Standards Institute. 2010. Performance standards for antimicrobial susceptibility testing: 20th informational supplement document M100-S20. Wayne PA: Clinical and Laboratory Standards Institute CLSI, (2010).
Gaynes RP, Culver DH. Resistance to imipenem among selected gram-negative bacilli in the United States. Infect Control Hosp Epidemiol 1992; 13:10–4.
Sievert DM, Ricks P, Edwards JR, Schneider A, Patel J, Srinivasan A, Kallen A, Limbago B, Fridkin S; National Healthcare Safety Network (NHSN) Team and Participating NHSN Facilities. Antimicrobial- resistant pathogens associated with healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol 2013;34(1):1-14.
Senbayrak Akcay S, Inan A, Cevan S, Ozaydın AN, Cobanoglu N, Ozyurek SC, Aksaray S. Gram-negative bacilli causing infections in an intensive care unit of a tertiary care hospital in Istanbul, Turkey. J Infect Dev Ctries 2014;14:8(5):597-604.
Ulusal Sağlık Hizmeti İlişkili Enfeksiyonları Sürveyans Sistemi. 2010-2014 yılı etken dağılım ve antibiyotik direnç raporları. infline.saglik.gov.tr.
Balkan II, Aygün G, Aydın S, Mutcalı SI, Kara Z, Kuşkucu M, Midilli K, Şemen V, Aras S, Yemişen M, Mete B, Özaras R, Saltoğlu N, Tabak F, Öztürk R.Blood stream infections due to OXA-48-like carbapenemase- producing Enterobacteriaceae: Treatment and survival. Int J Infect Dis 2014;26:51-6.
Schwaber MJ, Klarfeld-Lidji S, Navon-Venezia S, Schwartz D, Leavitt A, Carmeli Y. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother 2008;52 (3):1028-33.
Chusri S, Silpapojakul K, McNeil E, Singkhamanan K, Chongsuvivatwong V. Impact of antibiotic exposure on occurrence of nosocomial carbapenem-resistant Acinetobacter baumannii infection: A case control study. J Infect Chemother 2015;21(2):90-5.
McGregor JC, Kim PW, Perencevich EN, Bradham DD, Furuno JP, Kaye KS, Fink JC, Langenberg P, Roghmann MC, Harris AD. Utility of the chronic disease score and Charlson Comorbidity Index as comorbidity measures for use in epidemiologic studies of antibiotic-resistant organisms. Am J Epidemiol 2005;161(5):483-93.
DalBen MF, Basso M, Garcia CP, Costa SF, Toscano CM, Jarvis WR, Lobo RD, Oliveira MS, Levin AS. Colonization pressure as a risk factor for colonization by multiresistant Acinetobacter spp and carbapenem- resistant Pseudomonas aeruginosa in an intensive care unit. Clinics (Sao Paulo) 2013;68 (8):1128-33.
Tijet N, Sheth PM, Lastovetska O, Chung C, Patel SN, Melano RG. Molecular characterization of Klebsiella pneumoniae Enterobacteriaceae in Ontario, Canada, 2008-2011. PloS One 2014;9(12):e116421. (KPC)-producing
Köseoğlu Eser O, Altun Uludağ H, Ergin A, Boral B, Sener B, Hasçelik G. Carbapenem resistance in ESBL positive Enterobacteriaceae isolates causing invasive infections. Mikrobiyol Bul 2014;48(1):59-69.
Zavascki AP, Bulitta JB, Landersdorfer CB. Combination therapy for carbapenem-resistant Gram-negative bacteria. Expert Rev Anti Infect Ther 2013;11(12):1333-53.
van Duin D, Kaye KS, Neuner EA, Bonomo RA. Carbapenem-resistant Enterobacteriaceae: A review of treatment and outcomes. Diagn Microbiol Infect Dis 2013;75(2):115-20.
Paul M, Carmeli Y, Durante-Mangoni E. Combination therapy for carbapenem resistant Gram-negative bacteria. J Antimicrob Chemother 2014;69(9):2305-9.