Home | About IJMPO | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Advertise | Contact us |  Login 
Indian Journal of Medical and Paediatric Oncology
Search Article 
  
Advanced search 
 

 Table of Contents      
ORIGINAL ARTICLE
Year : 2013  |  Volume : 34  |  Issue : 2  |  Page : 85-88  

Review of clinical profile and bacterial spectrum and sensitivity patterns of pathogens in febrile neutropenic patients in hematological malignancies: A retrospective analysis from a single center


1 Department of Medical and Pediatric Oncology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
2 Department of Microbiology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India

Date of Web Publication6-Aug-2013

Correspondence Address:
Arun B Karanwal
A/8 Swagat Bunglows Part 3, New C.G. Road, Chandkheda, Ahmedabad - 382 424, Gujarat
India
Login to access the Email id

Source of Support: Department of Medical and Paediatric Oncology and Department of Microbiology Gujarat Cancer and Research Institute, Ahmedabad, Conflict of Interest: None


DOI: 10.4103/0971-5851.116184

Rights and Permissions
  Abstract 

Background: The aim of this study was to study clinical profile with bacterial spectrum and susceptibility patterns of pathogens in culture positive febrile neutropenic (FN) patients of hematological malignancies. Materials and Methods: We retrospectively reviewed the medical records of 23 hematological malignancy patients admitted with chemotherapy induced febrile neutropenia with culture positive results, at our institute between June 2011 and December 2011. Results: A total of 23 patients were studied 12 males and 11 females, with a median age of 35 years. Most common diagnosis was acute leukemia (78%) with the majority of patients developing febrile neutropenia during the induction phase of treatment. Most common presenting symptoms were fever, cough, dyspnea, and diarrhea. Primary site of infection was not found in 47% of patients while the rest had lung, gastro-intestinal and skin/soft-tissue infection. Overall 23 organisms were isolated during the study period, from blood (56%), sputum (46%), stool (23%), and nasal swab from one patient. Gram negative bacteria accounted for 78% of organisms while gram positive organisms accounted for 22% of the total isolates. The most common organisms were: Escherichia coli (43%), Staphylococcus aureus (22%), Pseudomonas aeruginosa (17.4%) and Klebsiella pneumonia (17.4%). Antibiotic sensitivity patterns of these bacteria were studied. Gram negative bacterial infections were associated with higher mortality (89%). Conclusions: Induction phase of treatment in acute leukemia is the major cause of FN in hematological malignancies at our institute and gram negative organisms are the predominant organisms with E. coli as major isolate while S. aureus represents the most common gram positive organism. Amikacin and cefoperazone/sulbactum appears to be initial antibiotic appropriate to cover most gram negative pathogens while vancomycin to be added for suspected gram positive infections. FN represents a major cause of morbidity and mortality in hematological malignancy patients, high index of suspicion and early empirical antibiotics with supportive care are main interventions to reduce high mortality for these patients. Antibiotics should be modified according to culture sensitive report as soon as possible.

Keywords: Antibiotics, febrile neutropenia, hematological malignancies


How to cite this article:
Karanwal AB, Parikh BJ, Goswami P, Panchal HP, Parekh BB, Patel KB. Review of clinical profile and bacterial spectrum and sensitivity patterns of pathogens in febrile neutropenic patients in hematological malignancies: A retrospective analysis from a single center. Indian J Med Paediatr Oncol 2013;34:85-8

How to cite this URL:
Karanwal AB, Parikh BJ, Goswami P, Panchal HP, Parekh BB, Patel KB. Review of clinical profile and bacterial spectrum and sensitivity patterns of pathogens in febrile neutropenic patients in hematological malignancies: A retrospective analysis from a single center. Indian J Med Paediatr Oncol [serial online] 2013 [cited 2020 Jan 26];34:85-8. Available from: http://www.ijmpo.org/text.asp?2013/34/2/85/116184


  Introduction Top


Febrile neutropenia (FN) is a common complication of cancer treatment. With the development of more aggressive chemotherapy regimens for hematological malignancies, the survival of these patients has improved. At the same time, these patients frequently succumb to febrile neutropenia, which is the major cause of morbidity and mortality. Studies have reported that 48-60% of patients admitted with febrile neutropenia have an infection, which can be life-threatening as well. [1]

Over the past decade, there has been a considerable change in the spectrum and antibiotic susceptibility patterns of pathogens causing infection in FN patients. Knowledge of locally prevalent pathogens and their sensitivities is essential as it helps to guide antimicrobial therapy in neutropenic patients. [2] The most effective empirical antimicrobial regimen must be rapidly administered to FN patients as delay in the initiation of treatment may result in septicemic shock and thus increase mortality.

To have an insight into the clinical profile of these FN patients as well as spectrum of antimicrobial susceptibility pattern, we have done this retrospective study.


  Materials and Methods Top


All clinical and microbiological data were collected retrospectively from FN patients admitted at our institute between June 2011 and December 2011. The inclusion criteria's include hematological malignancy patients having FN and culture positive report. Patient population consisted of both adults and pediatrics with acute and chronic leukemia, myelodysplastic syndrome (MDS), multiple myeloma and other malignancies. FN was defined as fever greater than 38.5°C on one occasion and with an absolute neutrophil count (ANC) of less than 0.5 × 10 9 /L. Cultures were taken from blood in all cases and from urine, stool, tracheal aspirate, sputum or wound depending upon identifiable focus of infection. Blood cultures were processed using the Bactec blood culture system. Organisms were identified according to routine bacteriological procedures. Antibiotic susceptibility testing was performed by disc diffusion method. Results of these were interpreted according to the Clinical Laboratory Standards Institutes guidelines.


  Results Top


A total of 23 (12 males and 11 females) patients with chemotherapy induced FN were analyzed. [Table 1] shows the characteristics of these patients. The mean age of the study population was 35 years (range 16-63 years). Majority of patients were of acute leukemia (78%), acute myeloid leukemia (AML) 48% (11/23), acute lymphoblastic leukemia (ALL) 30% (7/23), one patient each of chronic myeloid leukemia (CML), MDS, multiple myeloma, and two patients of other diagnosis. Majority of patients had developed FN during the induction phase of acute leukemia treatment. Most common presenting symptoms were fever, cough, dyspnea and diarrhea.
Table 1: Baseline patients characteristics

Click here to view


[Table 2] shows major laboratory findings. Median ANC was 120/μl, majority of patients also had anemia (median Hb 6.8 g/l) and thrombocytopenia (median platelet count 12000/μl). Primary site of infection was not found in 47% of patients while the rest had lung, gastrointestinal tract and skin/soft-tissue infection. Overall 23 organisms were isolated during the study period, from blood (56%), sputum (46%), stool (23%), and nasal swab from one patient. [Table 3] shows various isolated bacteria with respect to the site of isolation. Gram negative bacteria accounted for 78% of organisms while gram positive organisms accounted for 22% of the total isolates. The most common organisms were: Escherichia coli (43%), Staphylococcus aureus (22%), Pseudomonas aeruginosa (17.4%) and Klebsiella pneumonia (17.4%). [Figure 1] and [Figure 2] shows sensitivity and resistance patterns of these four organisms respectively. Majority of E. coli strains were sensitive to amikacin, ciprofloxacin and tigecycline while the majority were resistant to piperacillin/tazobactum (P/T), ceftazidime and cefazolin. P. aeruginosa strains were highly sensitive to amikacin, cefoperazone/sulbactum (C/Su) and ciprofloxacin while they were resistant to tigecycline and tobramycin. For K. pneumonia main sensitive antibiotics were amikacin and tigecycline and resistant antibiotics were P/T, cefazolin and ciprofloxacin. Lastly for S. aureus main sensitive antibiotics were vancomycin, linezolid and gentamicin and resistant one were penicillin, erythromycin and ciprofloxacin.
Figure 1: Antibiotic sensitivity pattern in bacterial isolates

Click here to view
Figure 2: Antibiotic resistance pattern in bacterial isolates

Click here to view
Table 2: Major investigation findings

Click here to view
Table 3: Site of culture positive with the organism

Click here to view


Empirical antifungal were used in 15 patients, amphotericin (7), fluconazole (6) and voriconazole (2).

Most common antibiotics used were P/T, amikacin, imipenum/cilastatin (I/C) and C/Su, most were empirically started. Other than antibiotics, patient also received growth factors (7/23) for an average of 11 days, Packed Cell Volume support (15/23) with an average of 5 units and platelet support (15/23) with an average of 17 units. [Table 4] shows outcomes of our patients. Median duration of neutropenia was 8.5 days, median duration of hospital stay was 16 days with recovery in 61% and mortality due sepsis in 39%. Gram negative bacterial infections were associated with higher mortality (89%). [Table 5] shows mortality in respect to different bacteria.
Table 4: Outcome of patients

Click here to view
Table 5: Mortality with respect to isolated organism

Click here to view



  Discussion Top


Over the past 25 years, there has been a shift in the microbiological spectrum from gram negative to gram positive organisms at many cancer centers. [3] The possible reasons for this shift are better control of gram negative infections with newer ultra-broad spectrum antibiotics, fluoroquinolone prophylaxis, and increase use of long dwelling intravenous devices. [4],[5] This study demonstrates that gram negative organisms are still the predominant pathogens causing bacteremia in FN patients. The spectrum of bacterial isolates in our study is similar to what has been reported in both local and international studies. Coagulase negative staphylococci were the most commonly isolated gram positive organisms. [3],[6] E. coli was the most frequently isolated gram negative pathogen. [3],[7]

This study shows that C/Su and amikacin may represent current best empirical antibiotics for suspected gram negative infections while for gram positive infections; vancomycin and linezolid may play the same role. As soon as the culture sensitivity report comes, antibiotics should be modified for best outcomes. Currently, P/T, amikacin, I/C and C/Su are the most common empirical antibiotics used at our institute.

Our study shows that FN is one of the major causes of morbidity and mortality in patients of hematological malignancies. These patients may not present with any obvious source of infection except blood stream infection. Hence, in all patients suspected of FN, blood culture sensitivity should be sent if possible before the first dose of antibiotics. Furthermore, these patients generally have associated anemia and thrombocytopenia, which should be adequately supported with blood transfusion. Growth factors should be used except in situations like during induction regimens of acute leukemia.


  Conclusions Top


Induction phase of treatment of acute leukemia are the major cause of FN in hematological malignancies at our institute and gram negative organisms are the predominant organisms with E. coli as major isolate while S. aureus represents the most common gram positive organism. Amikacin and C/Su appears to be initial antibiotic appropriate to cover most gram negative pathogens while vancomycin to be added for suspected gram positive infections. FN represents a major cause of morbidity and mortality in hematological malignancy patients, high index of suspicion and early empirical antibiotics with supportive care are main interventions to reduce high mortality for these patients. Antibiotics should be modified according to culture sensitive report as soon as possible. Continuous surveillance of the spectrum of locally prevalent pathogens and their susceptibility patterns is essential for formulation of therapeutic regimens for chemotherapy induced FN patients.


  Acknowledgments Top


Dr. Shilin N. Shukla (MD, Hon director Gujarat Cancer and Research Institute Ahmedabad), Dr. Pankaj M. Shah (MD, Ex Director Gujarat Cancer and Research Institute Ahmedabad), Dr. Shailesh S. Talati (MD, Professor Department of Medical and Paediatric Oncology, Gujarat Cancer and Research Institute Ahmedabad), Dr. Asha N. Anand (MD, DM professor Department of Medical and Paediatric Oncology, Gujarat Cancer and Research Institute Ahmedabad), nursing staff and patients of Gujarat Cancer and Research Institute.

 
  References Top

1.Cattaneo C, Quaresmini G, Casari S, Capucci MA, Micheletti M, Borlenghi E, et al. Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: Results of a prospective study on 823 patients at a single institution. J Antimicrob Chemother 2008;61:721-8.  Back to cited text no. 1
    
2.Sigurdardottir K, Digranes A, Harthug S, Nesthus I, Tangen JM, Dybdahl B, et al. A multi-centre prospective study of febrile neutropenia in Norway: Microbiological findings and antimicrobial susceptibility. Scand J Infect Dis 2005;37:455-64.  Back to cited text no. 2
    
3.Blahová J, Králiková K, Krcméry V Sr, Babálová M, Menkyna R, Glosová L, et al. Monitoring of antibiotic resistance in bacterial isolates from bacteremic patients. J Chemother 2004;16:269-72.  Back to cited text no. 3
    
4.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. 4
    
5.Viscoli C, Varnier O, Machetti M. Infections in patients with febrile neutropenia: Epidemiology, microbiology, and risk stratification. Clin Infect Dis 2005;40:S240-5.  Back to cited text no. 5
    
6.Baskaran ND, Gan GG, Adeeba K, Sam IC. Bacteremia in patients with febrile neutropenia after chemotherapy at a university medical center in Malaysia. Int J Infect Dis 2007;11:513-7.  Back to cited text no. 6
    
7.Kirby JT, Fritsche TR, Jones RN. Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients: Report from the chemotherapy alliance for neutropenics and the control of emerging resistance program (North America). Diagn Microbiol Infect Dis 2006;56:75-82.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


This article has been cited by
1 Pharmacometric Approaches to Personalize Use of Primarily Renally Eliminated Antibiotics in Preterm and Term Neonates
Mélanie Wilbaux,Aline Fuchs,Janko Samardzic,Frédérique Rodieux,Chantal Csajka,Karel Allegaert,Johannes N. van den Anker,Marc Pfister
The Journal of Clinical Pharmacology. 2016;
[Pubmed] | [DOI]
2 Clinical and Microbiological Profile of Pathogens in Febrile Neutropenia in Hematological Malignancies: A Single Center Prospective Analysis
M. Taj,T. Farzana,T. Shah,S. Maqsood,S. S. Ahmed,T. S. Shamsi
Journal of Oncology. 2015; 2015: 1
[Pubmed] | [DOI]
3 Epidemiological and mycological characteristics of candidemia in patients with hematological malignancies attending a tertiary-care center in India
Eshani Dewan,Debasis Biswas,Barnali Kakati,S.K. Verma,Aarti Kotwal,Aroma Oberoi
Hematology/Oncology and Stem Cell Therapy. 2015; 8(3): 99
[Pubmed] | [DOI]
4 Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children
Frederique Rodieux,Melanie Wilbaux,Johannes N. van den Anker,Marc Pfister
Clinical Pharmacokinetics. 2015; 54(12): 1183
[Pubmed] | [DOI]
5 Micro-organisms Associated with Febrile Neutropenia in Patients with Haematological Malignancies in a Tertiary Care Hospital in Eastern India
Prakas Kumar Mandal,Suman Kumar Maji,Tuphan Kanti Dolai,Rajib De,Shyamali Dutta,Sandeep Saha,Maitreyee Bhattacharyya
Indian Journal of Hematology and Blood Transfusion. 2014;
[Pubmed] | [DOI]
6 Hitna stanja u onkologiji i hematologiji | [Emergiencies in oncology and haematology]
Dobrila-Dintinjana, R., Redžović, A., Valković, T., Ilijić, V., Vanis, N.
Medicina Fluminensis. 2013; 49(4): 405-413
[Pubmed]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
   Abstract
  Introduction
   Materials and Me...
  Results
  Discussion
  Conclusions
  Acknowledgments
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed2847    
    Printed57    
    Emailed0    
    PDF Downloaded636    
    Comments [Add]    
    Cited by others 6    

Recommend this journal