ABSTRACT

Objectives:

Bacterial bloodstream infections with resistant pathogens in patients with hematological malignancies are increasing due to the more use of new chemotherapeutic agents and prophylactic antibiotics. In this study, it was aimed to determine the epidemiology and resistance rates of gram-negative bacterial pathogens isolated from blood cultures of febrile neutropenic patients with hematological malignancies in order to help the correct administration of empirical antibiotics and to limit resistance.

Materials and Methods:

Antibiotic susceptibility of gram-negative bacteria, which were grown in the blood cultures of hematological febrile neutropenic patients in a tertiary university hospital between 2019 and 2021 and determined as bloodstream infection, was retrospectively investigated.

Results:

Between January 1, 2019 and December 31, 2021, a total of 388 gram-negative isolates, which were isolated from blood cultures and evaluated as bloodstream infection, in the febrile neutropenia attacks of patients with hematological malignancies hospitalized in the hematology service were evaluated, and the most common isolated pathogen was found to be Klebsiella spp. (41.7%). When evaluated in terms of multi-drug resistance, it was determined that Klebsiella spp. was in the first and Acinetobacter spp. was in the second place. When evaluated in terms of piperacillin-tazobactam susceptibility, which we frequently use in the empirical treatment of febrile neutropenic patients, 70.3% of Klebsiella spp., 37.7% of Escherichia coli, 86% of Acinetobacter spp. and 67.5% of Pseudomonas spp. were found to be resistant to piperacillin-tazobactam. Carbapenem resistance was also found to be between 29% and 80%.

Conclusion:

It is noteworthy that all gram-negative strains were highly resistant to piperacillin-tazobactam, which is used as empirical treatment of febrile neutropenia attacks, and that carbapenem resistance was found at a substantial rate. Considering these data may contribute to reducing morbidity and mortality while arranging empirical treatment guidelines and antibiotic management programs in febrile neutropenia attacks seen in hematological malignancy patients both in our hospital and in Turkey.

Keywords: Febrile Neutropenia, Hematologic Malignancy, Antimicrobial Sensitivity, Multidrug Resistance

References

Villafuerte-Gutierrez P, Villalon L, Losa JE, et al. Treatment of febrile neutropenia and prophylaxis in hematologic malignancies: a critical review and update. Adv Hematol. 2014;2014:986938 Erratum in: Adv Hematol 2019;2019.

Kokkayil P, Agarwal R, Mohapatra S, et al. Bacterial profile and antibiogram of blood stream infections in febrile neutropenic patients with haematological malignancies. J Infect Dev Ctries. 2018;12:442-447. https://doi.org/10.3855/jidc.9725.

Gedik H, Simşek F, Kantürk A, et al. Bloodstream infections in patients with hematological malignancies: which is more fatal—cancer or resistant pathogens? Ther Clin Risk Manag. 2014;10:743-752.

Blennow O, Ljungman P. The challenge of antibiotic resistance in haematology patients. Br J Haematol. 2016;172:497-511.

Garcia-Vidal C, Cardozo-Espinola C, Puerta-Alcalde P, et al. Risk factors for mortality in patients with acute leukemia and bloodstream infections in the era of multiresistance. PLoS One. 2018;13:e0199531.

Tang Y, Wu X, Cheng Q, et al. Inappropriate initial antimicrobial therapy for hematological malignancies patients with gram-negative bloodstream infections. Infection. 2020;48:109-116.

Righi E, Peri AM, Harris PN, et al. Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis. J Antimicrob Chemother. 2017;72:668-677.

Fentie A, Wondimeneh Y, Balcha A, et al. Bacterial profile, antibiotic resistance pattern and associated factors among cancer patients at University of Gondar Hospital, Northwest Ethiopia. Infect Drug Resist. 2018;11:2169-2178.

Rolston KV. Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia. Clin Infect Dis. 2005;40(Suppl 4):S246.

Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011; 52:e56.

Moghnieh R, Kanafani ZA, Abi Hanna P, et al. 2016 Lebanese Society of Infectious Diseases and Clinical Microbiol- ogy guidelines on the management of febrile neutropenia in adult cancer patients in the era of growing antimicrobial resistance. Lebanese Medical Journal. 2017;103:1-20.

Diekema DJ, Hsueh P-R, Mendes RE, Pfaller MA, Rolston KV, Sader HS, et al. The microbiology of bloodstream infection: 20-year trends from the SENTRY antimicrobial surveillance program. Antimicrob Agents Chemother. 2019;63:e00355-19.

The European Committee on Antimicrobial Susceptibility Testing (EUCAST), 2019. Breakpoint tables for interpretation of MICs and zone diameters. Version 9.0, 1 Jan - 31 Dec, 2019

The European Committee on Antimicrobial Susceptibility Testing (EUCAST), 2020. Breakpoint tables for interpretation of MICs and zone diameters. Version 10.0, 1 Jan - 31 Dec, 2020

The European Committee on Antimicrobial Susceptibility Testing (EUCAST), 2021. Breakpoint tables for interpretation of MICs and zone diameters. Version 11.0, 1 Jan - 31 Dec, 2021

Vasoo S, Cunningham SA, Kohner PC, et al. Comparison of a novel, rapid chromogenic biochemical assay, the carba NP test, with the modified Hodge test for detection of carbapenemase-producing gram-negative bacilli. J Clin Microbiol. 2013;51:3097-3101.

Gupta A, Singh M, Singh H, et al. Infections in acute myeloid leukemia: An analysis of 382 febrile episodes. Med Oncol. 2010;27:1037 45.

Hamidi AA, Başaran S, Çağatay AA, et al. Febril Nötropenik Hastalarda Bakteriyemi Etkeni Olabilecek Patojenler, Direnç Durumu ve Hastaların Özellikleri Klimik Dergisi. 2009;22:88-91.

Demirkaya MH, Yeşilkaya A, Akcil-Ok M, et al. İmmunokompromize Hastalarda Bakteriyemi Etkenleri. Klimik Dergisi. 2017;30: 32-35.

Çam B ve Ulu Kılıç A. Erişkin Hematoloji ve Kemik İliği Transplantasyonu (KİT) Ünitelerinde Yatan Hematolojik Maligniteli Hastalarda Gelişen Kan Dolaşımı Enfeksiyonlarının İncelenmesi. Kırşehir Ahi Evran Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi. 2020;1:158-169.

Gafter-Gvili A, Fraser A, Paul M, et al. Cochrane gynaecological, neuro-oncology and orphan cancer group. Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy. Cochrane Database Syst Rev. 2012;1:CD004386.

Mikulska M, Averbuch D, Tissot F, et al. Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. J Infect. 2018;76:20-37.

Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America clinical practice guide-line update. J Clin Oncol. 2018;36:1443-1453.

Satlin MJ, Jenkins SG, Walsh TJ. The global challenge of carbapenem-resistant Enterobacteriaceae in transplant recipients and patients with hematologic malignancies. Clin Infect Dis. 2014;58:1274-1283.

Micozzi A, Gentile G, Minotti C, et al. Carbapenem-resistant Klebsiella pneumoniae in high-risk hematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias. BMC Infect Dis. 2017;17:203.

Evaluation of the Distribution and Antimicrobial Susceptibility of Gram-negative Bacteria Isolated from Blood Cultures in Heamatologic Febrile Neutropenia Attacks

ABSTRACT

References