The Impact of Modifying Empirical Antibiotic Therapy Based on Intestinal Colonization Status on Clinical Outcomes of Febrile Neutropenic Patients

다국어 초록 (Multilingual Abstract)

Background: This paper aimed to inspect factors affecting febrile neutropenia patients with hematologic malignancies. The intestinal colonization rate of extended-spectrum betalactamase-producing Enterobacteriaceae (ESBL-E) and carbapenem-resistant Enterobacteriaceae (CRE) was assessed. The rate of subsequent ESBL-E and CRE bacteremia correlated with corresponding bacterial colonization was evaluated. Further, the risk factors for ESBL-E and CRE intestinal colonization were examined. Finally, the impact of rectal swab screening combined with adapted empirical antibiotic therapy on the mortality rate of patients with febrile neutropenia was assessed.
Materials and Methods: Febrile neutropenia patients underwent rectal swabs and collection of blood culture specimens upon admission. Empirical treatment was subsequently modified according to rectal swab results if necessary. Bacteremia patients were treated according to blood culture results. Explorative forward-stepwise logistic regression analyses were used to identify risk factors for ESBL-E and CRE fecal carriage and mortality.
Results: In total, 201 rectal swabs and 402 blood samples were collected from 163 patients during 201 febrile neutropenia episodes. Of these episodes, 38 (18.90%) were colonized with ESBL-E and 30 (14.92%) with CRE. Bloodstream infections developed in 29/201 (14.42%) episodes. Only bacteremia episodes caused by Gram-negative bacilli were included in our analysis. The development of Gram-negative-rod bacteremia was observed in eight out of 38 (21.05%) ESBL-E colonized episodes and four out of 30 (13.33%) CRE-colonized episodes.
A BSI developed in three out of 38 (7.89%) ESBL-E colonized episodes, and two out of 30 (6.66%) CRE-colonized episodes developed BSI with the respective organism. Multivariate analysis identified previous quinolone use as the only independent risk factor for fecal colonization of multi-drug-resistant (MDR) Enterobacteriaceae (ESBL-E and CRE) (odds ratio, 17.09; 95% confidence interval, 5.29 - 55.18; P <0.0001). No significant association was observed between ESBL-E and CRE carriage and increased risk of developing subsequent bacteremia. No significant differences were detected between groups receiving modified and non-modified treatments in duration of hospitalization or antibiotic therapy (univariate analysis) and 28-day mortality rate (logistic regression).
Conclusion: Quinolone exposure was a major risk factor for ESBL-E and CRE fecal carriage.
Performing rectal swab screening for MDR Enterobacteriaceae and modifying empirical antibiotic therapy accordingly did not improve clinical outcomes of febrile neutropenia patients.

참고문헌 (Reference)

1 Narimatsu H, "Value of pretransplant screening for colonization of Pseudomonas aeruginosa in reduced-intensity umbilical cord blood transplantation for adult patients" 86 : 449-451, 2007

2 Kontopoulou K, "The clinical significance of carbapenem-resistant Klebsiella pneumoniae rectal colonization in critically ill patients: from colonization to bloodstream infection" 68 : 326-335, 2019

3 Reddy P, "Screening for extended-spectrum β-lactamase-producing Enterobacteriaceae among high-risk patients and rates of subsequent bacteremia" 45 : 846-852, 2007

4 Arnan M, "Risk factors for, and clinical relevance of, faecal extended-spectrum β-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic patients with haematological malignancies" 30 : 355-360, 2011

5 Borer A, "Risk factors for developing clinical infection with carbapenem-resistant Klebsiella pneumoniae in hospital patients initially only colonized with carbapenem-resistant K pneumoniae" 40 : 421-425, 2012

6 Giannella M, "Risk factors for carbapenem-resistant Klebsiella pneumoniae bloodstream infection among rectal carriers: a prospective observational multicentre study" 20 : 1357-1362, 2014

7 Bodey GP, "Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia" 64 : 328-340, 1966

8 Christophy R, "Prevalence, antibiotic susceptibility and characterization of antibiotic resistant genes among carbapenem-resistant Gram-negative bacilli and yeast in intestinal flora of cancer patients in North Lebanon" 10 : 716-720, 2017

9 Baaity Z, "Prevalence of extended spectrum β lactamases (ESBL) in E. coli at AlAssad Teaching Hospital" 10 : 2433-2436, 2017

10 Schwaber MJ, "Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality" 52 : 1028-1033, 2008

11 Clinical and laboratory standards institute (CLSI), "Performance standards for antimicrobial susceptibility testing" CLSI 2011

12 Menzo SL, "New insight on epidemiology and management of bacterial bloodstream infection in patients with hematological malignancies" 7 : e2015044-, 2015

13 Kassem DF, "Multidrug-resistant pathogens in hospitalized Syrian children" 23 : 166-168, 2017

14 Blijlevens NM, "Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview" 25 : 1269-1278, 2000

15 Demiraslan H, "Is surveillance for colonization of carbapenem-resistant gram-negative bacteria important in adult bone marrow transplantation units?" 45 : 735-739, 2017

16 Liss BJ, "Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies" 40 : 613-619, 2012

17 Srinivasan A, "Increasing prevalence of nasal and rectal colonization with methicillin-resistant Staphylococcus aureus in children with cancer" 55 : 1317-1322, 2010

18 Kluytmans JA, "Extendedspectrum β-lactamase-producing Escherichia coli from retail chicken meat and humans: comparison of strains, plasmids, resistance genes, and virulence factors" 56 : 478-487, 2013

19 Rhee MS, "Evaluation of consumer-style cooking methods for reduction of Escherichia coli O157:H7 in ground beef" 66 : 1030-1034, 200

20 Averbuch D, "European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia" 98 : 1826-1835, 2013

21 Freifeld AG, "Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america" 52 : e56-e93, 2011

22 Schechner V, "Asymptomatic rectal carriage of blaKPC producing carbapenem-resistant Enterobacteriaceae: who is prone to become clinically infected?" 19 : 451-456, 2013

23 Taplitz RA, "Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update" 36 : 3043-3054, 2018

24 Abbara A, "Antimicrobial Drug Resistance among Refugees from Syria, Jordan" 23 : 885-886, 2017

25 Vehreschild MJ, "A multicentre cohort study on colonization and infection with ESBL-producing Enterobacteriaceae in highrisk patients with haematological malignancies" 69 : 3387-3392, 2014