Piperacillin / Tazobactam in-vitro Activity in Escherichia coli and Klebsiella pneumoniae Strains with Extended Spectrum Beta-Lactamase Production

Abstract

Piperacillin-tazobactam (TZP) is a frequently preferred agent for the treatment of infections caused by Gram-negative bacteria producing expanded spectrum beta-lactamase (ESBL). However, there are some controversies about the efficacy of Piperacillin-tazobactam in severe infections caused by ESBL producing bacteria. In this study, we aimed to determine the efficacy of TZP in ESBL-positive bacteria isolated from the samples sent to our laboratory. Our medical microbiology laboratory included 548 ESBL producing Escherichia coli and Klebsiella pneumoniae strains from blood, urine, wounds, tracheal aspirate samples from outpatient and outpatient clinics. VITEC 2® was used for bacterial identification, antibiotic susceptibility study and ESBL detection. Our study included 307 (56%) E. coli, 241 (%43.9) K. pneumoniae isolates. When the resistance rates of TZP of isolates are examined; The resistance rate of TZP in E. coli strains was 44.6% and the highest resistance was detected in tracheal aspirates with 47.6%.  In K. peumoniae strains, the resistance rate of TZP was found to be 41%. While there are not enough studies showing the efficacy of TZP in infections caused by ESBL positive bacteria, the existing studies show that the efficacy of these antibiotics changes according to infection site and severity. There is no consensus between CLSI and EUCAST regarding the TZP result notification. Therefore, there is a need for more extensive work in this regard and a reevaluation of the outcome report of the TZP.

Genişlemiş Spektrumlu Beta-laktamaz Üreten Escherichia coli ve Klebsiella pneumoniae Suşlarında Piperasilin/Tazobaktam İnvitro Etkinliği

Öz

Piperasilin-tazobaktam (TZP), genişletilmiş spektrumlu beta-laktamaz (GSBL) üreten Gram-negatif bakterilerin  neden olduğu enfeksiyonların tedavisi için sıklıkla tercih edilen bir ajandır. Bununla birlikte, GSBL üreten bakterilerin neden olduğu ciddi enfeksiyonlara Piperasilin-tazobaktamın etkinliği hakkında tartışmalar vardır. Bu çalışmada, laboratuvara gönderilen örneklerden izole edilen GSBL pozitif bakterilerde TZP'nin etkinliğini belirlemeyi amaçladık. Servis ve poliklinik hastalarına ait kan, idrar, yara, trakeal aspirat örneklerinden izole edilen 548 GSBL pozitif Escherichia coli ve Klebsiella pneumoniae suşu çalışmaya dahil edildi. Bakteri tanımlaması, antibiyotik duyarlılık testleri ve GSBL tespitinde VİTEK 2® otomatize sistemi kullanıldı. Çalışmamıza dahil edilen izolatların 307’si (%56) E. coli, 241’i (%43,9) K. pneumoniae suşu idi. İzolatların TZP direnç oranları incelendiğinde; E. coli suşlarında TZP direnç oranı %44,6 olarak saptanırken en yüksek direnç %47,6 ile trakeal aspirat örneklerinde saptandı. K. peumoniae suşlarında ise TZP direnç oranı %41 olarak bulundu. GSBL pozitif bakterilerin neden olduğu enfeksiyonlarda TZP'nin etkinliğini gösteren yeterli çalışma bulunmamakla birlikte, mevcut çalışmalar bu antibiyotiklerin etkinliğinin enfeksiyon bölgesine ve şiddetine göre değiştiğini göstermektedir. PRP sonuç bildirimi ile ilgili CLSI ve EUCAST arasında bir fikir birliği yoktur. Bu nedenle, bu konuda daha kapsamlı bir çalışmaya ve TZP'nin sonuç raporunun yeniden değerlendirilmesine ihtiyaç vardır.

Anahtar Kelimeler

• Piperasilin-tazobaktam,genişlemiş spektrumlu beta-laktamaz,Escherichia coli

References

1. Seo YB, Lee J, Kim YK, Lee SS, Lee J, Kim HY, Uh Y et all. Randomized controlled trial of piperacillin tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum betalactamase-producing Escherichia coli. BMC Infectious Diseases. 2017; 17:404. DOI 10.1186/s12879-017-2502-x
2. Ofer-Friedman H, Shefler C, Sharma S, Tirosh A, Tal-Jasper R, Kandipalli D. Carbapenems Versus Piperacillin- Tazobactam for Bloodstream Infections of Nonurinary Source Caused by Extended- Spectrum Beta-Lactamase–Producing Enterobacteriaceae. Infect Control Hosp Epidemiol. 2015;36(8):981-5.
3. De L’E´toile-Morel S, Cheng MP, Cheng AP, McDonald EG, Lee TC. Piperacillin-tazobactam use in GSBL Escherichia coli bacteremia:Should reporting be revised? JAMMI.2018 3:1,doi:10.3138/jammi.3.1.05.
4. Wayne P. Performance standards for antimicrobial susceptibility testing, 28th ed. CLSI supplement M100.Clinical and Laboratory Standards Institute; 2018.
5. Leclercq R, Canto´n R, Brown DF, et al. EUCAST expert rules in antimicrobial susceptibility testing. Clin Microbiol Infect. 2013;19(2):141–60.
6. Schuetz AN, Reyes S, Tamma PD. Point-Counterpoint: Piperacillin-Tazobactam Should Be Used To Treat Infections with Extended-Spectrum-Beta-Lactamase-Positive Organisms. J Clin Microbiol. 2018;56(3). doi: 10.1128/JCM.01917-17.
7. Guet-Revillet H, Tomini E, Emirian A, Join-Lambert O, Lecuyer H, Zahar JR, Jullien V. Piperacillin/tazobactam as an alternative antibiotic therapy to carbapenems in the treatment of urinary tract infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae: an in silico pharmacokinetic study. Int J Antimicrob Agents. 2017 Jan;49(1):62-66.
8. Gavin PJ, Suseno MT, Thomson RB, Gaydos JJM, Pierson CL, Halstead DC, Aslanzadeh J et all. Clinical Correlation of the CLSI Susceptibility Breakpoint for Piperacillin-Tazobactam against Extended-Spectrum-_-Lactamase-Producing Escherichia coli and Klebsiella Species. Antimicrob Agents Chemother; 2006: 50(6):2244–47

9. Şen P, Yula E, Demirdal T, Kaya S, Nemli SA, Demirci M. Solunum yollarından izole edilen genişlemiş spektrumlu ve indüklenebilir beta-laktamaz üreten bakterilerin direnç oranları. Ortadoğu tıp derg.2017;9 (4): 170-176.
10. Tamma PD, Han JH, Rock C, Harris AD, Lautenbach E, Hsu AJ, et all. for the Antibacterial Resistance Leadership Group. Carbapenem Therapy Is Associated With Improved Survival Compared With Piperacillin- Tazobactam for Patients With Extended- Spectrum β-Lactamase Bacteremia. Treatment of GSBL Bacteremia. Clin Infect Dis. 2015; 60: 1319-25.
11. Rodrı´guez-Ban˜o J, Navarro MD, Retamar P, et al. b-lactam/b-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum b-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis. 2012;54(2):167–74.
12. Vardakas KZ, Tansarli GS, Rafailidis PI, Falagas MB.Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum b-lactamases: a systematic review and meta-analysis. J Antimicrob Chemother. 2012; 67(12):2793–803.
13. Retamar P, López-Cerero L, Muniain MA, Pascual Á, Rodríguez-Baño J,the GSBL-REIPI/GEIH Group. Impact of the MIC of Piperacillin-Tazobactam on the Outcome of Patients with Bacteremia Due to Extended-Spectrum-_-Lactamase-Producing Escherichia coli. Antimicrob Agents Chemother.2013:57(7): 3402–04
14. Harris PN, Peleg AY, Iredell J, Ingram PR, Miyakis S, Stewardson AJ, Rogers BA, McBryde ES, Roberts JA, Lipman J,Athan E, Paul SK, Baker P, Harris-Brown T, Paterson DL. Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp (the MERINO trial): study protocol for a randomised controlled trial. BioMed Central. 2015: 16:24
15. Sönmez U, Çalık Ş, Çayıröz MU, Olut AI, Arı A, Tosun S, Yiş R. Genişlemiş spektrumlu beta-laktamaz salgılayan Klebsıella pneumonıae ve Escherıchıa coli’ye bağlı bakteriyemilerde mortalite ile ilişkili risk faktörlerinin belirlenmesi ve ampirik piperasilin tazobaktam ile karbapenem tedavisi sonuçlarının karşılaştırılması ANKEM Derg 2018;32(1):1-8