Erişkin Yoğun Bakım Ünitelerinde Karbapenem Dirençli Klebsiella pneumoniae ile Kolonizasyon/Enfeksiyon Gelişimi ve Karbapenemaz Tiplerinin Dağılımı

Abstract

Karbapenem dirençli Enterobacteriaceae üyelerinin neden olduğu enfeksiyonların sıklığı tüm dünyada giderek artmakta olup mortalite oranları oldukça yüksektir. Bu kökenler ile oluşan enfeksiyonların ve kolonize hastaların hızlı tespiti, enfeksiyon kontrol protokollerinin uygulanması açısından oldukça önemlidir. Çalışmamızda erişkin yoğun bakım ünitelerinde yatan hastalarda karbapenem dirençli Klebsiella pneumoniae kökenleri ile gelişen kolonizasyon/enfeksiyon oranları ve karbapenemaz tiplerinin araştırılması amaçlanmıştır. Bu çalışmaya erişkin yoğun bakım ünitelerinde yatan hastalardan Haziran-Aralık 2017 tarihleri arasında rektal sürüntü örneklerinden ve klinik örneklerden izole edilen karbapenem dirençli K.pneumoniae (KD-Kp) kökenleri dahil edilmiştir. Kökenlerin antibiyotik duyarlılıkları VITEK2 otomatize sistemi ile çalışılmıştır. Karbapenemazların fenotipik tespitinde NG CARBA-5 immunokromayöntemi üreticinin önerileri doğrultusunda çalışılmıştır. Karbapenemaz genlerinin (OXA-48, IMP, VIM, KPC, NDM) varlığı spesifik primerler kullanılarak PCR yöntemi ile araştırılmıştır. Çalışma süresi içerisinde 344 hastaya ait tarama kültüründen 51 adet ve aynı döneme ait klinik örneklerden 30 adet KD-Kp üremiştir. Hastaların en az üçte birinde birden fazla gen pozitifliği gözlemlenmiştir. Enfeksiyon gelişen 17 hastanın geçmiş üç ay içerisinde bu mikroorganizma ile kolonize olduğu saptanmıştır. Enfeksiyon saptanan 4 hastanın tarama kültürleri negatif iken 9 hastada tarama kültürü olmaksızın KD-Kp enfeksiyonu gelişmiştir. Buna göre yoğun bakım ünitelerimizde kolonizasyon/enfeksiyon oranı %33,3 saptanmıştır. Yoğun bakım ünitelerimizde OXA-48 ve NDM türü enzimler % 60’lar düzeyindedir. İlginç olan daha önceki yıllarda gözlemlemediğimiz KPC tipi enzimin hem klinik hem de tarama kültürlerinden saptanmış olmasıdır. Yoğun bakım ünitelerimizde enfeksiyon/kolonizasyon oranı azımsanmayacak düzeyde olup kolonize hastaların yaklaşık üçte birinde enfeksiyon gelişebileceği belirlenmiştir.

Keywords

• Karbapenemaz
• Klebsiella pneumoniae
• kolonizasyon/enfeksiyon

Development of Colonization/Infection with Carbapenem Resistant Klebsiella pneumoniae and Distribution of Carbapenemase Types in Adult Intensive Care Units

Abstract

The incidence of infections caused by carbapenem-resistant Enterobacteriaceae is increasing worldwide and, mortality rates are high. Rapid detection of infections and colonized patients with these strains is very important for the implementation of infection control protocols. In this study, we aimed to investigate the colonization/infection rates and carbapenemase types due to carbapenem-resistant Klebsiella pneumoniae in patients hospitalized in adult intensive care units. Carbapenem-resistant K.pneumoniae (CRKP) strains isolated from the rectal swab and clinical samples between JuneDecember 2017 from patients hospitalized in adult intensive care units were included in this study. Antibiotic susceptibility of the strains was studied by VITEK2 automated system. In the phenotypic determination of carbapenemases, NG CARBA-5 immunochromatographic method was studied according to the manufacturer’s recommendations. The presence of carbapenemase genes (OXA-48, IMP, VIM, KPC, NDM) was investigated by PCR method using specific primers. During to study period, 51 CR-Kp from the screening culture of 344 patients and 30 CR-Kp from clinical samples were produced. More than one gene positivity was observed in at least one-third of the patients. Seventeen patients who developed infection were colonized with this microorganism in the past three months. Four patients with infection had negative screening cultures, while nine patients developed CRKP infection without screening culture. Accordingly, colonization/infection rate in our intensive care units was determined as 33.3%. In our intensive care units, OXA-48 and NDM enzymes are 60 %. Interestingly, the KPC type enzyme, which we did not observe in previous years, was detected from both clinical and screening cultures. The infection / colonization rate in our intensive care units is not negligible and, approximately one third of colonized patients may develop the infection.

Keywords

• Carbapenemase
• colonization/infection
• Klebsiella pneumoniae

References

1. Aktaş Z, Kayacan CB, Schneider I, Can B, Midilli K, Bauernfeind A. Carbapenem-hydrolyzing oxacillinase, OXA-48, persists in Klebsiella pneumoniae in Istanbul, Turkey. Chemotherapy. 2008;54(2):101-6.
2. Banach DB, Francois J, Blash S et al. Active surveillance for carbapenem-resistant Enterobacteriaceae using stool specimens submitted for testing for Clostridium difficile. Infect Control Hosp Epidemiol. 2014; 35(1):82-4.
3. Bhargava A, Hayakawa K, Silverman E et al. Risk factors for colonization due to carbapenem-resistant Enterobacteriaceae among patients exposed to longterm acute care and acute care facilities. Infect Control Hosp Epidemiol. 2014;35(4):398-405.
4. Calfee D, Jenkins SG. Use of active surveillance cultures to detect asymptomatic colonization with carbapenem-resistant Klebsiella pneumoniae in intensive care unit patients. Infect Control Hosp Epidemiol. 2008;29(10):966-8.
5. Cole JM, Schuetz AN, Hill CE, Nolte FS. Development and evaluation of a real-time PCR assay for detection of Klebsiella pneumoniae carbapenemase genes. J Clin Microbiol. 2009;47(2):322-6.
6. Dautzenberg MJ, Wekesa AN, Gniadkowski M et al. The association between colonization with carbapenemase-producing Enterobacteriaceae and overall ICU mortality: an observational cohort study. Crit Care Med. 2015;43(6):1170-7.
7. Debby BD, Ganor O, Yasmin M et al. Epidemiology of carbapenem-resistant Klebsiella pneumoniae colonization in an intensive care unit. Eur J Clin Microbiol Infect Dis. 2012;31(8):1811-7.
8. Dickstein Y, Edelman R, Dror T, Hussein K, Bar-Lavie Y, Paul M. Carbapenem-resistant Enterobacteriaceae colonization and infection in critically ill patients: a retrospective matched cohort comparison with noncarriers. J Hosp Infect. 2016;94(1):54-9.

9. European Committee on Antimicrobial Susceptibility Testing 2018. Breakpoint tables for interpretation of MICs and zone diameters Version 8.0 http://www.eucast.org/clinical_breakpoints
10. Lee CR, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol. 2016;13(7):895.
11. McConville TH, Sullivan SB, Gomez-Simmonds A, Whittier S, Uhlemann AC. Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of infection and 90-day mortality in critically ill patients, an observational study. PLoS One. 2017;12(10):e0186195.
12. Papadimitriou-Olivgeris M, Marangos M, Fligou F et al. Risk factors for KPC-producing Klebsiella pneumoniae enteric colonization upon ICU admission. J Antimicrob Chemother. 2012;67(12):2976-81.
13. Perry JD, Naqvi SH, Mirza IA, Alizai SA et al. Prevalence of faecal carriage of Enterobacteriaceae with NDM-1 carbapenemase at military hospitals in Pakistan, and evaluation of two chromogenic media. J Antimicrob Chemother. 2011;66(10):2288-94.
14. Pitout JD, Gregson DB, Poirel L, McClure JA, Le P, Church DL. Detection of Pseudomonas aeruginosa producing metallo-beta-lactamases in a large centralized laboratory. J Clin Microbiol. 2005;43(7): 3129-35.
15. Risk assessment on the spread of carbapenemaseproducing Enterobacteriaceae (CPE) through patient transfer between healthcare facilities, with special emphasis on cross-border transfer. ECDC Technical Report (2011). https://ecdc.europa.eu/en/publications-data
16. Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin Microbiol Rev. 2012;25(4):682-707.
17. Vidal-Navarro L, Pfeiffer C, Bouziges N, Sotto A, Lavigne JP. Faecal carriage of multidrug-resistant Gram-negative bacilli during a non-outbreak situation in a French university hospital. J Antimicrob Chemother. 2010;65(11):2455-8.
18. Wiener-Well Y, Rudensky B, Yinnon AM et al. Carriage rate of carbapenem-resistant Klebsiella pneumoniae in hospitalised patients during a national outbreak. J Hosp Infect. 2010;74(4):344-9.
19. Zhao ZC, Xu XH, Liu MB, Wu J, Lin J, Li B. Fecal carriage of carbapenem-resistant Enterobacteriaceae in a Chinese university hospital. Am J Infect Control. 2014;42(5):e61-4.