Resistance patterns of gram negative bacteria in urinary tract infections and efficacy of empirical treatment in noncomplicated cases: Retrospective cohort study of 2180 women

Abstract

Aim: Community and hospital acquired urinary tract infections (UTI) are the most common bacterial infections in all age groups. In this study, the women diagnosed UTI, which complicated and uncomplicated, were referred to outpatient clinics between 2011 and 2015 were selected. The suitability of empirical antimicrobial therapy prescribed with resistance patterns of Gram negative bacteria isolated from these patients was investigated. 

Methods: UTI complaining and urine culture ≥10⁵ cfu / ml of bacteria that women aged 18-65 were comprised the study group. HIS (Hospital Information System Software) was scanned for these patients and uncomplicated and complicated UTI distinction was made according to the criteria set by Infectious Diseases Society of America (IDSA, 2016). Of the 2180 patients studied, 836 were complicated and 896 were noncomplicated. Identification of Gram negative isolates in urine culture; Conventional methods and Matrix-Assisted Laser Desorption and Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS), (Biotyper, Bruker, Germany) systems were used. The antimicrobial susceptibilities of the isolated strains from 2011 to 2014 were determined according to the Clinical Laboratory Standards Institute (CLSI) and the isolated strains in 2015 were determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). 

Results: The distribution of 2180 female patients (18 to 65 years old) was urology polyclinic (68%), family medicine, infectious disease and physical medicine and rehabilitation polyclinics (19.1%), and emergency medicine polyclinic (12.6%). E. coli (84%), K. pneumonia / oxytoca (7%) and Enterobacter spp (2.6%) were the most frequently detected agents in the uncomplicated UTIs, while complicated UTI E. coli (91%), K. pneumonia / oxytoca (5.7%) and P. aeruginosa (1%) were found to be the first, second and third in the patients. Quinolones were prescribed 18.2%, phosphomycin 16.7%, nitrofurantoin 15.6%, nitrofurantoin and phosphomycin combined 16.3%, second generation oral cephalosporins 9.6% and third generation oral cephalosporins 10.7%. Resistance to quinolones, the most commonly prescribed antibiotic, was found in 19% of E. coli, 21% of Klebsiella spp., 13% of Enterobacter spp. and 9% of Proteus spp. 

Conclusion: When these prescriptions were compared with the results of antimicrobial susceptibility, it was observed that 38 (14%) were incompatible with the sensitivity results. It was found that 42% of cefuroxime prescriptions, 28% of quinolone prescriptions and 17% of ceftriaxone prescriptions were incompatible with the antibiogram results.

Keywords

• Antimicrobial resistance,Empirical therapy,Urinary tract infections,Escherichia coli,Klebsiella spp

Üriner sistem enfeksiyonlarında gram negatif bakterilerin direnç paternleri ve komplike olmayan hastalarda ampirik tedavinin uygunluğu: 2180 kadın hastada retrospektif kohort çalışma

Öz

Amaç: Toplum ve hastane kaynaklı üriner sistem enfeksiyonları (ÜSE), tüm yaş gruplarında en sık karşılaşılan bakteriyel enfeksiyonlardır. Bu çalışmada 2011-2015 yılları arasında polikliniklere ÜSE şikayetiyle başvuran hastalardan izole edilen Gram negatif bakterilerin direnç paternleri ile bu hastalara reçetelenen ampirik antimikrobiyal tedavinin uygunluğunun araştırıldı.

Yöntemler: ÜSE şikayetiyle başvuran ve idrar kültüründe ≥10⁵ kob/ml bakteri üremesi olan 18-65 yaş arası kadın hastalar çalışma grubunu oluşturdu. HBYS (Hastane Bilgi Yazılım Sistemi)’nden bu hastaların dosyası taranarak Infectious Diseases Society of America (IDSA, 2016) tarafından belirlenen kriterler doğrultusunda komplike olmayan ve komplike ÜSE ayrımları yapıldı. Buna göre 2180 hastanın 836’sı komplike ÜSE tanısı alırken, 896’sının nonkomplike ÜSE tanısı aldığı tesbit edildi. İdrar kültüründe izole edilen Gram negatif izolatların identifikasyonu; konvansiyonel yöntemler ve Matrix-Assisted Laser Desorption and İonization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS), (Biotyper, Bruker, Almanya) sistemleri ile yapıldı. İzole edilen suşların antimikrobiyal duyarlılıkları 2011-2014 yılları için Clinical Laboratory Standards Institute (CLSI), 2015 yılı için ise The European Committee on Antimicrobial Susceptibility Testing (EUCAST) önerilerine göre belirlendi. 

Bulgular: ÜSE şikayetiyle çalışmaya alınan 18-65 yaş arası 2180 kadın hastanın poliklinik dağılımı; %68 Üroloji, %19,1 Aile Hekimliği pol., Enfeksiyon pol ve Fizik Tedavi ve Rehabilitasyon pol. ve %12,6 Acil pol. idi. Komplike olmayan ÜSE’lerde 1., 2. ve 3. sırada en çok tespit edilen etken sırasıyla E. coli (%84), K. pneumoni/oxytoca (%7) ve Enterobacter spp (%2,6) iken, komplike ÜSE’li hastalarda 1., 2. ve 3. sırada E. coli (%91), K. pneumoni/oxytoca (%5,7) ve P. aeruginosa (%1) tespit edildi. Hastalara reçete edilen antimikrobiyallere bakıldığında; kinolonların %18,2 oranında, fosfomisin %16,7, nitrofurantoin %15,6, nitrofurantoin ve fosfomisin kombine olarak %16,3 oranında, 2. kuşak oral sefalosporinlerin %9,6 ve 3. kuşak oral sefalosporinlerin ise %10,7 oranında reçetelendiği saptandı. Ayaktan tedavi edilen hastalara en sık reçete edilen antibiyotik olan kinolonlara direnç, E.coli’de %19, Klebsiella spp.’de %21, Enterobacterspp.’de %13, Proteus spp’de % 9 olarak bulundu. 

Sonuç: Bu reçetelerin antimikrobiyal duyarlılık sonuçları ile uyumuna bakıldığında ise, 38(%14)’inin duyarlılık sonuçları ile uyumsuz olduğu gözlendi. Sefuroksim reçetelerinin %42, kinolon reçetelerinin %28, seftriakson reçetelerinin ise %17 oranında antibiyogram sonucu ile uyumsuz olduğu saptandı.

Anahtar Kelimeler

• Antimikrobiyal direnç,Üriner sistem enfeksiyonu,Ampirik tedavi,Escherichia coli,Klebsiella spp

Kaynakça

1. 1. Turktan M, Ak O, Erdem H, Ozcengiz D, Hargreaves S, Kaya S, et al. Community acquired infections among refugees leading to Intensive Care Unit admissions in Turkey. Int J Infect Dis. 2017 May;58:111-4.
2. 2. Mody L, Juthani-Mehta M. Urinary Tract Infections in Older Women JAMA. 2014 Feb 26; 311(8): 844–54.
3. 3. Erdoğan Aydos S, Yavuzdemir S, Nohutcu Y, Cavus I. In Vitro Sensitivity of Bacteria to Various Antibiotics, Obtained from Women Suffering From Cystitis. J Turk Soc Obstet Gynecol. 2006;3(2):118-21.
4. 4. Kattan JN, Gordon S. Acute Uncomplicated Urinary Tract Infections. available at: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/urinary-tract-infection/]
5. 5. Beveridge LA, Davey PG, Phillips G, McMurdo ET. Optimal management of urinary tract infections in older people. Clin Interv Aging. 2011;6:173–80.
6. 6. Guidelines on urological infections. European Association of Urology 2014 http://www.uroweb.org/gls/pdf/19%20Urological%20infections_LR.pdf date of access: 29.05.2017
7. 7. Gupta G, Hooton T, Naber K, Wullt B, Colgan R, Miller L, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.
8. 8. Gul S, Ecemis E, Kacmaz B, Kaygusuz S, Ayaslıoğlu E, Kılıc D. Antibiotic Susceptibility of Bacteria Isolated from Urine Culture. KUTFD. 2014;16(3):17-21.

9. 9. Zengin K, Tanık S, Albayrak S, Kaba M, Pirincci N. The Urinary System Infectious Agents and Their Antibiotics Susceptibilities in Van District. Bozok Med J. 2014;4(1):1-5.
10. 10. Aypak C, Altunsoy A, Duzgun N. Empiric Antibiotic Therapy In Acute Uncomplicated Urinary Tract Infections And Fluoroquinolone Resistance: A Prospective Observational Study. Annals of Clinical Microbiology and Antimicrobials. 2009;8:27.
11. 11. Kahan NR, Chinitz DP, Waitman DA, Kahan E. Empiric treatment of uncomplicated UTI in women: wasting money when more is not better. Journal of Clinical Pharmacy and Therapeutics. 2004,29:437-41.
12. 12. Velasco E, Noll I, Espelage W, Ziegelmann A, Krause G, Eckmanns T. A survey of outpatient antibiotic prescribing for cystitis. Dtsch Arztebl Int. 2012 Dec;109(50):878-84.
13. 13. Gozukucuk R, Cakıroğlu B, Nas Y. Antibiotic Susceptibility of Escherichia coli Strains Isolated in Community Acquired Urinary Tract Infection, JAREM. 2012;2:101-3.
14. 14. Durmus G. Investigation Of The Risk Factors For Extended Spectrum Beta Lactamase Production In The Patients With Upper Urinary Tract Infections In Infectious Diseases Unit, Master Thesis, Trakya Univ. Medicine Faculty, Department of Disease of Infectious and Clinical Microbiology, 2009.
15. 15. Duman Y, Bozkurt I, Tekerekoglu MS. Investigation of Antibiotic Resistance and ESBL-Presence of Community Acquired Escherichia Coli Strains, Isolated from UTI in Afsin State Hospital. Medicine Science. 2014;3(3):1408-18.
16. 16. Yılmaz N, Agus N, Bayram A, Samlıoğlu P, Sirin MC, Karaca Derici Y, Yılmaz Hancı S. Antimicrobial susceptibilities of Escherichia coli isolates as agents of community-acquired urinary tract infection (2008-2014). Turk J Urol. 2016;42(1):32-6.
17. 17. Goldstein FW, Multicentre Study Group. Antibiotic Susceptibility of Bacterial Strains Isolated from Patient with CommunityAcquired Urinary Tract Infections in France. Eur J Clin Microbiol Infect Dis. 2000;19:112-7.
18. 18. Arslan H, Azap OK, Ergonul O, Timurkaynak F. Urinary Tract Infection Study Group. Risk factors for ciprofloxacin resistance among Escherichia coli strains isolated from community-acquired urinary tract infections in Turkey. J Antimicrob Chemother. 2005;56:914-8.
19. 19. Gulcan A, Aslanturk A,Gulcan E. The Microorganisms Isolated From Urine Culture and Their in Vitro Antibiotic Susceptibility. Abant Med J. 2012;1(3):129-135.
20. 20. Aykan S B, Ciftci I H. Antibiotic Resistance Patterns of Escherichia coli Strains Isolated from Urine Cultures in Turkey: A Meta-Analysis, Mikrobiyol Bul. 2013;47(4): 603-18.
21. 21. Mengeloglu FZ, Demircan F, Oduncu MK. Evaluating of in vitro Susceptibilities of Escherichia coli Strains Isolated from Urine Cultures to Fosfomycine. ANKEM. 2011;25(2):99102.
22. 22. Uyanık MH, Hancı H, Yazgı H. In-vitro Activity of Fosfomycin Trometamol and some other Antibiotics to Escherichia coli Strains Isolated from Community-acquired Urinary Tract Infections ANKEM. 2009;23(4)172-6.
23. 23. Tasbakan MI, Pullukcu H, Yamazhan T, Arda B, Ulusoy S. Comparison of In-Vitro Activity of Fosfomycin and other Antibacterials in Escherichia coli Strains Isolated from Community Acquired Urinary Tract Infections. ANKEM. 2004;18(4):216-9.
24. 24. Karagoz G, Kadanalı A, Dede B ve ark. The frequency of extended-spectrum beta-lactamase and the rate of antibiotic resistance in Escherichis coli strains. TAF Prev Med Bull. 2013;12(3):291-6
25. 25. Aytac O, Mumcuoglu I, Cetin F, Aksoy A, Aksu N. The antibiotic susceptibility changes of the Escerichia coli strains isolated from community acquired urinary tract infections in adults according to the years (2010-2014). Turkısh Bulletin Of Hygiene And Experimental Biology. 2015;72(4):273–80.
26. 26. Kandemir O, Akdağ A, Kurt AO. Antibiotic Susceptibility of Bacterial Strains Isolated From Patients with Community Acquired Urinary Tract Infections in Mersin. TAF Prev Med Bull. 2012;11(5):589-98.
27. 27. Calıskan E, Dede A, Altınoz A, Biten G, Kas E. The Evaluation of Resistance Rates to Various Antibiotics and Extended Spectrum Beta-lactamase Positivity of Esherichia coli and Klebsiella spp. Strains Isolated from Outpatients with Urinary Tract Infection. ANKEM. 2015;29(2);47-53.
28. 28. Kashef N, Esmaeeli Djavid G, Shahbazi S. Antimicrobial susceptibility patterns of community-acquired uropathogens in Tehran, Iran. J Infect Dev Ctries. 2010;4:202-6.
29. 29. Bahadin J, Teo SS, Mathew S. Aetiology of community-acquired urinary tract infection and antimicrobial susceptibility patterns of uropathogens isolated. Singapore Med J. 2011;52(6):415.