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ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 4  |  Page : 456-458
 

Frequency of bacterial isolates and pattern of antimicrobial resistance in patients with hematological malignancies: A snapshot from tertiary cancer center


1 Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
2 Department of Microbiology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India

Date of Web Publication1-Feb-2016

Correspondence Address:
M Sengar
Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.175387

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 » Abstract 

Background: Infections are the most important cause of mortality in patients with high-risk febrile neutropenia. Emergence of multi-drug resistant organisms (MDROs) has become a major challenge for hemato-oncologists. Knowledge of the prevalent organisms and their antimicrobial sensitivity can help deciding the empirical therapy at individual centers and allows timely measures to reduce the risk of antimicrobial resistance. Aims: To evaluate the frequency of bacterial isolates from all the samples and the pattern of bacterial bloodstream infections and incidence of MDROs. Settings And Design: This is a retrospective analysis from a tertiary care cancer center. Materials And Methods: From January to June 2014 information on all the samples received in Department of Microbiology was collected retrospectively. The data from samples collected from patients with hematological cancers were analyzed for types of bacterial isolates and antimicrobial sensitivity. Results: A total of 739 isolates were identified with 67.9% of isolates being Gram-negative. The predominant Gram-negative organisms were Escherichia coli, Psuedomonas spp. and Klebsiella spp. Among the bacterial bloodstream infections, 66% were Gram-negative isolates. MDROs constituted 22% of all isolates in blood cultures. Incidence of resistant Gram-positive organisms was low in the present dataset (methicillin resistant Staphylococcus aureus and vancomycin-resistant enterococci-1.3%). Conclusions: The analysis reconfirms the Gram-negative organisms as the predominant pathogens in bacteremia seen in patients with hematological cancers. The high frequency of multi-drug resistance in the dataset calls for the need of emergency measures to curtail further development and propagation of resistant organisms.


Keywords: Bacterial bloodstream infections, febrile neutropenia, multidrug resistant organism


How to cite this article:
Sengar M, Kelkar R, Jain H, Biswas S, Pawaskar P, Karpe A. Frequency of bacterial isolates and pattern of antimicrobial resistance in patients with hematological malignancies: A snapshot from tertiary cancer center. Indian J Cancer 2014;51:456-8

How to cite this URL:
Sengar M, Kelkar R, Jain H, Biswas S, Pawaskar P, Karpe A. Frequency of bacterial isolates and pattern of antimicrobial resistance in patients with hematological malignancies: A snapshot from tertiary cancer center. Indian J Cancer [serial online] 2014 [cited 2019 Dec 14];51:456-8. Available from: http://www.indianjcancer.com/text.asp?2014/51/4/456/175387



 » Introduction Top


Emergence of multi-drug resistant organisms (MDROs) has raised an alarm across medical fraternity, and hemato-oncologists are among the most affected. Infections with MDRO's in immunocompromised hosts (hematological malignancies) are associated with very high mortality rates and thus negate the potential survival benefits of intensive chemotherapy regimens.[1],[2] Prevention of further development of antimicrobial resistance needs to be addressed as an emergency given the lack of any new antibiotics (available or in pipeline) against the MDRO's.[3] One of the most important steps toward prevention of newer and widespread antimicrobial resistance is formulation and adherence to antibiotic stewardship program in each hospital. This requires identification of prevalent causative bacteria and their antimicrobial sensitivity patterns in one's own center to develop institutional antibiotic guidelines. This is particularly relevant in patients with hematological malignancy in whom the treatment of febrile neutropenia is mostly empirical and infection associated mortality is much higher as opposed to other cancers or nononcology patients. The likelihood of MDRO carries strong impact on decision of escalation or de-escalation of antibiotic therapy in high-risk febrile neutropenia.[4] In order to understand the frequency of MDRO's, we carried out a retrospective analysis to evaluate the frequency and in vitro antimicrobial susceptibility patterns of bacterial isolates from blood and other samples collected from patients with hematological malignancies, who were being treated for neutropenic/nonneutropenic fever at our center from January to June 2014.


 » Materials and Methods Top


In this retrospective analysis, we retrieved information from Department of Microbiology at our center on all samples that were submitted from January 2014 to June 2014. Among all the samples, we identified the ones collected from patients with hematological cancers (nontransplant) as part of workup for febrile neutropenia or nonneutropenic fever. The samples included peripheral blood, blood collected from peripherally inserted central catheter, urine, stool, sputum or bronchoalveolar lavage (BAL). The bacterial isolates from these samples were identified by routine biochemical reactions. An analysis of the microbiological spectrum and the antibiotic sensitivity pattern of the bacterial isolates were performed. The in vitro antibiotic sensitivity pattern of these isolates was determined by the Kirby Bauer's disc diffusion method. Choice of antibiotic disks used was determined by Clinical and Laboratory Standards Institute (CLSI) guidelines.[5] Extended spectrum beta-lactamase (ESBL) production was confirmed by CLSI recommendations using cephalosporin-clavulanate combination disks. A difference of ≥5 mm between zone diameter of either of the cephalosporin disks and their respective cephalosporin-clavulanate disk was taken to be phenotypic confirmation of ESBL production. We used cefotaxime (30 μg), ceftazidime (30 μg) and ceftazidime/clavulanic acid (30 μg/10 μg) disks for ESBL determination. Carbapenem resistance was reported as per the CLSI guidelines. Methicillin resistant Staphylococcus aureus (MRSA) were detected with cefoxitin (30 μg) disks. Vancomycin resistance was confirmed by minimal inhibitory concentrations with the E-test.

Statistical analysis

The data were analyzed with SPSS version 18.0 Chicago: SPSS Inc. The variables were analyzed using descriptive statistics for the frequency of various isolates and the MDRO.


 » Results Top


A total of 18,918 samples were sent to department of microbiology from January to June 2014. About 21% (3998/18918) were from patients with hematological cancers. Among these samples, the majority were peripheral blood (1988/3998-49.7%) and blood from PICC (675/3998-17%). Samples from other sites were sent based on clinical signs and symptoms. The remaining samples included urine (5.4%), sputum and BAL (7.1%) and others (wound swab, stool, pleural fluid; 20.8%).

Among 3998 samples, 739 bacterial isolates (18.4%) were detected; 67.2% being Gram-negative isolates. The frequency of bacterial isolates from different samples was variable; blood-9.4%, urine-11.4%, sputum and BAL-62% and others-34.7%.

Sixty-six percent of all bacterial bloodstream infections (252) were caused by Gram-negative organisms [Table 1]. The most common isolates were Escherichia coli (19%) and Pseudomonas spp. (18.7%) followed by Klebsiella spp. (16.7%), Acinetobacter spp. (7.1%) and Enterobacter spp. (4.8%). A total of 33.7% were Gram-positive isolates. The most common isolate was coagulase negative Staphylococcus (CONS-20%) followed by S. aureus (5.5%), Streptococcus spp. (3.9%), and Enterococcus spp. (3.6%).
Table 1: Distribution of bacterial bloodstream infection isolates


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In urine samples, Gram-negative organisms constituted 84% of all isolates (25) with E. coli being the most common organism (60%). Enterococcus spp. (4/25–16%) was the only Gram-positive organism seen in urine cultures.

Among all the bacterial isolates (176) from sputum, Gram-negative organism constituted 57% of all isolates. The most common organism being Klebsiella spp. (20.4%) followed by Pseudomonas spp. (14.2%), E. coli (10.8%), Acinetobacter spp. (3.4%) and Stenotrophomonas maltophilia (2.8%). The most common Gram-positive isolates were group A beta-hemolytic streptococci (40.9%) followed by S. aureus (1.7%).

We analyzed all bacterial isolates to assess the prevalence of resistant organisms. Across all the samples, 497 Gram-negative organisms (67.2%) were isolated. Approximately, 25.7% of these organisms were MDROs and 41.4% were ESBL producers. The frequency of MDROs across different Gram-negative isolates is shown in [Table 2]. In Gram-positive isolates, MRSA and vancomycin-resistant enterococci (VRE) were 1.2% and 19% respectively. Analysis of bacterial bloodstream isolates for resistant organisms revealed 22% Gram-negative MDROs, 1.3% MRSA and 1.3% VRE. There were no pan-resistant (resistant to colistin/polymixin) organisms in any of the samples.
Table 2: Frequency of MDRO among all Enterobacteriacae isolates


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 » Discussion Top


In last decade, the epidemiology of bacteremia has changed in patients with febrile neutropenia with re-emergence of Gram-negative bacteremia and ever increasing antimicrobial resistance. The usage of quinolone prophylaxis, central venous catheters and misuse of antibiotics are the major factors responsible for this worrisome trend.[6],[7],[8] However, data from Indian studies have always shown Gram-negative organisms as the most common isolates in the setting of febrile neutropenia.[9] This is attributed partly to lack of antibiotic prophylaxis and infrequent use of central venous catheters. This study has reconfirmed predominance of Gram-negative bacteremia in patients with hematological malignancies with E. coli, Psuedomonas spp. and Klebsiella spp. being the main culprits. The predominant Gram-positive isolate was CONS that was most likely contaminant reflecting poor skin preparation prior to collection of blood culture samples. The major cause of concern reflected in this analysis is high frequency of MDROs (22%) in bacterial bloodstream infections. In addition, the other samples too showed a significant proportion of MDROs among the isolates. The implications of these findings are twofold: (1) Our patients with febrile neutropenia are at very high-risk of mortality if not treated appropriately, (2) in patients who present with hemodynamic instability should be treated with de-escalation approach of empirical antibiotics given the high rates of resistant organisms which may have colonized the host. In addition, a large proportion of patients will need empirical therapy as the rates of blood culture positivity are <10%. Given very low proportion of resistant Gram-positive isolates we should limit the empirical use of vancomycin or teicoplanin as it may add to the development of vancomycin resistance.

The similar situation is reflected in data from developed countries too. A prospective multi-center study involving hematology wards was conducted over 4 years showed resistance to third-generation cephalosporins in 36.9% of Enterobacteriacae isolates. The incidence of multi-drug resistance was 34.9% in Klebsiella spp. and 69.7% among Pseudomonas spp. The incidence of vancomycin resistance was <3%. The 21-day mortality was higher with Gram-negative bacterial bloodstream infections (16.9% vs. 5.6%) especially if infections were caused by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii.[10]

In the present analysis, significant proportions of sputum and other samples showed bacterial isolates that may reflect either colonization or invasive infections. In view of lack of corresponding information on clinical features and response to antibiotic therapy, it would be difficult to discriminate colonization from infection. This is the major limitation of this analysis. In addition, some of the samples may be from same patient collected during the same episode at different times or during different episodes and thus overestimating the prevalence of resistant organisms. In our study, the information on infection-related mortality is not available too. In spite of these limitations, the current data makes it imperative to institute the measures to tackle increasing antimicrobial resistance through appropriate antibiotic stewardship.


 » Conclusions Top


This study highlights the importance of continuous monitoring of prevalence and patterns of antimicrobial sensitivity in every center to guide antibiotic policies and measures needed to avert ever-growing antimicrobial resistance.

 
 » References Top

1.
Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: Mortality, length of hospital stay, and health care costs. Clin Infect Dis 2006;42 Suppl 2:S82-9.  Back to cited text no. 1
    
2.
Ramphal R. Changes in the etiology of bacteremia in febrile neutropenic patients and the susceptibilities of the currently isolated pathogens. Clin Infect Dis 2004;39 Suppl 1:S25-31.  Back to cited text no. 2
    
3.
Bow EJ. There should be no ESKAPE for febrile neutropenic cancer patients: The dearth of effective antibacterial drugs threatens anticancer efficacy. J Antimicrob Chemother 2013;68:492-5.  Back to cited text no. 3
    
4.
Bassetti M, Righi E. Multidrug-resistant bacteria: What is the threat? Hematology Am Soc Hematol Educ Program 2013;2013:428-32.  Back to cited text no. 4
    
5.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Eighteenth Informational Supplement. M100-S18. Wayne, PA: CLSI; 2008.  Back to cited text no. 5
    
6.
Cordonnier C, Herbrecht R, Buzyn A, Leverger G, Leclercq R, Nitenberg G, et al. Risk factors for Gram-negative bacterial infections in febrile neutropenia. Haematologica 2005;90:1102-9.  Back to cited text no. 6
    
7.
Satlin MJ, Calfee DP, Chen L, Fauntleroy KA, Wilson SJ, Jenkins SG, et al. Emergence of carbapenem-resistant Enterobacteriaceae as causes of bloodstream infections in patients with hematologic malignancies. Leuk Lymphoma 2013;54:799-806.  Back to cited text no. 7
    
8.
Quilty S, Kwok G, Hajkowicz K, Currie B. High incidence of methicillin-resistant Staphylococcus aureus sepsis and death in patients with febrile neutropenia at Royal Darwin Hospital. Intern Med J 2009;39:557-9.  Back to cited text no. 8
    
9.
Prabhash K, Medhekar A, Ghadyalpatil N, Noronha V, Biswas S, Kurkure P, et al. Blood stream infections in cancer patients: A single center experience of isolates and sensitivity pattern. Indian J Cancer 2010;47:184-8.  Back to cited text no. 9
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10.
Trecarichi EM, Pagano L, Candoni A, Pastore D, Cattaneo C, Fanci R, et al. Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: An Italian multicentre prospective survey. Clin Microbiol Infect 2014; Dec 3. pii: S1198-743X(14)00108-6. doi: 10.1016/j.cmi. 2014.11.022. [Epub ahead of print].  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2]

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