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 ╗  Abstract
 ╗ Introduction
 ╗  Materials and Me...
 ╗ Results
 ╗ Discussion
 ╗  References
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  Table of Contents  
Year : 2014  |  Volume : 51  |  Issue : 4  |  Page : 425-427

Review of spectrum and sensitivity of bacterial bloodstream isolates in children with malignancy: A retrospective analysis from a single center

1 Department of Medical Oncology, All Institute of Medical Sciences, New Delhi, India
2 Department of Microbiology, All Institute of Medical Sciences, New Delhi, India

Date of Web Publication1-Feb-2016

Correspondence Address:
S Bakhshi
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-509X.175363

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 ╗ Abstract 

Background: Febrile neutropenia is a life-threatening emergency in pediatric cancer patients. Its management is based on established guidelines that emphasize on prompt action. Consideration of local microbiologic spectrum and its susceptibility is pivotal in devising a rational protocol. AIMS: To study the spectrum of bacterial isolates and its antibiotic sensitivity profile in bloodstream infections (BSIs) of pediatric cancer patients. Settings And Design: Retrospective study. Materials And Methods: This study was conducted at a tertiary cancer center for pediatric cancer patients. Blood culture samples sent during the evaluation of patients with clinical diagnosis of febrile neutropenia during the year of 2013 were analyzed. The microbiological and antibiotic sensitivity patterns were studied. Results: A total of 27 isolates represented BSIs out of 412 blood cultures sent (6.5%). These were predominantly Gram-negative (92%) with Klebsiella contributing to the majority of them. Extended spectrum beta-lactamase production was seen in 59% of all isolates. Multidrug resistance phenotype was seen in 48%, extreme drug resistance in 32% and pan drug resistance in 16% of Gram-negative isolates. Klebsiella predominated in all of these isolates. Mortality resulted in 15% isolates, majorly contributed by Klebsiella. Colistin was the most sensitive antibiotic (75% sensitivity) and in significant number of cases the only salvage option. Conclusion: Gram-negative bacteria are the most common etiologic agents. The emergence of drug resistant strains of Klebsiella and the poor sensitivity of most of these strains to common first choice empiric agents is alarming. Low prevalence of Gram-positive organisms questions the routine use of empiric vancomycin.

Keywords: Antibiotic sensitivity, bloodstream infections, pediatric cancer

How to cite this article:
Reddy R, Pathania S, Kapil A, Bakhshi S. Review of spectrum and sensitivity of bacterial bloodstream isolates in children with malignancy: A retrospective analysis from a single center. Indian J Cancer 2014;51:425-7

How to cite this URL:
Reddy R, Pathania S, Kapil A, Bakhshi S. Review of spectrum and sensitivity of bacterial bloodstream isolates in children with malignancy: A retrospective analysis from a single center. Indian J Cancer [serial online] 2014 [cited 2021 Jul 28];51:425-7. Available from: https://www.indianjcancer.com/text.asp?2014/51/4/425/175363

 ╗ Introduction Top

Febrile neutropenia is a life-threatening emergency, the management of which rests on an initial thorough evaluation of the patient to determine the focus of infection and a rapid institution of broad spectrum antibiotics.[1],[2],[3] The choice of first-line antibiotics is usually empiric and does not await the results of the microbiologic studies. As it is, the focus remains obscure in a significant number of patients with a culture positive sepsis reported varyingly as 11–38%.[4],[5],[6] Hence, management is based on established guidelines with due consideration given to local microbiologic flora and its antibiotic sensitivity spectrum. There is a need to analyze the bloodstream infection (BSI) data at each center to make informed decisions regarding likely etiologic agents and rational use of antibiotics and antifungals. This study attempts to do the same in pediatric patients with cancer treated at our center.

 ╗ Materials and Methods Top

This study was a retrospective analysis of data obtained from a tertiary care cancer center for pediatric patients ≤18 years. It is our protocol to send a peripheral or central catheter blood specimen for culture at the outset and serially thereafter, in the evaluation of patients who develop or get admitted for febrile neutropenia. We analyzed all such samples sent for bacterial culture from our center to the central microbiology laboratory of our institute during the year of 2013. Among these, samples that represented BSI were identified. Standard microbiological reactions were used to identify the bacterial isolates.

Definition of antimicrobial resistance

Isolates were subjected to in vitro antibiotic susceptibility testing with Kirby Bauer's disc diffusion method and interpreted as per Clinical and Laboratory Standards Institute recommendations. Multidrug resistance (MDR) was defined as acquired nonsusceptibility to at least one agent in three or more antimicrobial categories; extreme drug resistance (XDR) was defined as nonsusceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e., bacterial isolates remain susceptible to only one or two categories) and pan drug resistance (PDR) was defined as nonsusceptibility to all agents in all antimicrobial categories.[7]

Statistical methods

Descriptive statistics was used to analyze the available data.

 ╗ Results Top

A total of 653 pediatric patients were treated with chemotherapy for various indications during the year 2013. In patients admitted for febrile neutropenia, 412 blood cultures were sent in total during this period. Of these, 27 patients had BSI documented, giving a blood culture positivity of 6.5%. The disease wise breakdown of the patients that we had treated and the incidence of BSI in each of them is depicted in [Table 1].
Table 1: Disease wise breakdown of bloodstream infection

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Bacterial isolates

Gram-negative organisms contributed to 25 out of the 27 positive cultures (92%). The majority of them were lactose fermenters (68%) with Klebsiella species (48%) being the most dominant among them. Of the nonlactose fermenters, Acinetobacter species were the most common isolates (n = 6; 22%).

Two Gram-positive isolates were seen in the whole year, one of them being Staphylococcus aureus and the other being Enterococcus. No methicillin resistant S. aureus or vancomycin resistant Enterococcus phenotype was seen respectively in these isolates.

Antimicrobial susceptibility pattern

The antibiotic sensitivity pattern of the Gram-negative bacterial isolates is depicted in [Table 2].
Table 2: Antibiotic sensitivity pattern of Gram-negative isolates

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Colistin was the most sensitive antibiotic among our isolates, with 75% of the isolates on which it was tested coming to be susceptible. Data of Colistin resistance have emerged only in Klebsiella species. These 4 isolates (15%) were pan-resistant to all drugs. The phenotypic distribution of resistant isolates is shown in [Table 3].
Table 3: Phenotypic distribution of Gram-negative isolates

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A total of 4 patients (15%) had died during the management of febrile neutropenia; 3 of them have grown Klebsiella and the other had grown Acinetobacter. All 3 of Klebsiella-related deaths were in the infections with pan-resistant isolate. The one with Acinetobacter showed a MDR phenotype.

 ╗ Discussion Top

Bloodstream infections are associated with increase in length of hospital stay, increase in the cost of care and cause significant morbidity and mortality.[8] The crude mortality associated with BSIs in cancer patients ranged from 18% to 42%.[6],[9]

There has been a substantial fluctuation in the spectrum of bloodstream isolates obtained from febrile neutropenic patients over the past five decades. Early in the beginning of cytotoxic therapy era, the causative pathogens were predominantly Gram-negative organisms. In the last three decades, a change in the trend was noted with the predominance of Gram-positive organisms owing to increased use of indwelling venous catheters.[10],[11],[12]

In our study, an overwhelming predominance of Gram-negative bacteria was seen (>90%). This observation is similar to other studies done from developing countries.[6],[13] In fact, two studies from India also found similar preponderance of Gram-negative organisms.[14],[15] The possible reasons for this are the low utilization of prophylactic antibiotics and lower use of indwelling venous catheters and portable devices. We do not use prophylactic antibiotics to prevent infection in any group of patients. A central venous catheter or a peripherally inserted central catheter line is placed routinely only during acute myeloid leukemia induction but not in other indications.

We had a predominance of lactose fermenters with Klebsiella being the most common organism. A relatively much lower incidence of Pseudomonas and other nonlactose fermenting Gram-negative Bacilli was seen in our series compared to other western as well as Indian literature.[6],[9],[16] A growing concern with our spectrum is the high incidence of resistant strains.

Extended spectrum beta-lactamase production was seen in more than half of the isolates and a significant proportion also exhibited the MDR/XDR phenotypes. A high representation of XDR isolates that showed sensitivity only to Colistin, also limits the therapeutic armamentarium and paves the way for the emergence of pan-resistant strains. These strains are turning out to be a concern for centers involved in care of these sick children and are associated with poor clinical outcomes.[17] The 4 deaths seen in this cohort at our center also exhibited the XDR/PDR phenotype, which underlines this fact.

High levels of resistance are noted for 3rd generation cephalosporins, aminoglycosides (33% sensitivity each) and piperacillin-tazobactam (26% sensitivity). These antibiotics feature routinely in our antibiotic policy. Carbapenems and Colistin are the only groups that have shown reasonable activity, but the level of resistance to these agents can only increase as their use continues to increase. The situation with Klebsiella isolates is especially grim with a very significant increase in XDR/PDR phenotype.

The very low rates of Gram-positive growths among our isolates have put a question mark over the routine use of vancomycin in antibiotic up gradation protocol. This probably warrants a revisit in this policy that adds both to the cost and the toxicity.

Strategies to counter the worsening scenario of antibiotic resistance are the need of the hour. Combination therapy given as empirical first line choice, routine use of prophylaxis and prolonged and frequent hospital admissions are shown to be associated with emergence of antibiotic resistance.[17],[18] The first factor probably needs a re-look in our policy. The evolution of the pathogens involved warrants an evolution in the practice guidelines also.[19]

These strategies require knowledge of the individual department's epidemiological profile and its continuous and updated monitoring. This should be every individual high volume center's prerogative.

 ╗ References Top

Serody JS. Fever in immunocompromised patients. N Engl J Med 2000;342:217-8.  Back to cited text no. 1
Maschmeyer G, Hiddemann W, Link H, Cornely OA, Buchheidt D, Glass B, et al. Management of infections during intensive treatment of hematologic malignancies. Ann Hematol 1997;75:9-16.  Back to cited text no. 2
Meckler G, Lindemulder S. Fever and neutropenia in pediatric patients with cancer. Emerg Med Clin North Am 2009;27:525-44.  Back to cited text no. 3
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
Madani TA. Clinical infections and bloodstream isolates associated with fever in patients undergoing chemotherapy for acute myeloid leukemia. Infection 2000;28:367-73.  Back to cited text no. 5
Lai HP, Hsueh PR, Chen YC, Lee PI, Lu CY, Lu MY, et al. Bacteremia in hematological and oncological children with febrile neutropenia: Experience in a tertiary medical center in Taiwan. J Microbiol Immunol Infect 2003;36:197-202.  Back to cited text no. 6
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18:268-81.  Back to cited text no. 7
Paganini HR, Aguirre C, Puppa G, Garbini C, Ruiz Guiñazú J, Ensinck G, et al. A prospective, multicentric scoring system to predict mortality in febrile neutropenic children with cancer. Cancer 2007;109:2572-9.  Back to cited text no. 8
Collin BA, Leather HL, Wingard JR, Ramphal R. Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin Infect Dis 2001;33:947-53.  Back to cited text no. 9
Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis 2003;36:1103-10.  Back to cited text no. 10
Zinner SH. Changing epidemiology of infections in patients with neutropenia and cancer: Emphasis on gram-positive and resistant bacteria. Clin Infect Dis 1999;29:490-4.  Back to cited text no. 11
Rubio M, Palau L, Vivas JR, del Potro E, Diaz-Mediavilla J, Alvarez A, et al. Predominance of gram-positive microorganisms as a cause of septicemia in patients with hematological malignancies. Infect Control Hosp Epidemiol 1994;15:101-4.  Back to cited text no. 12
Paul M, Gafter-Gvili A, Leibovici L, Bishara J, Levy I, Yaniv I, et al. The epidemiology of bacteremia with febrile neutropenia: experience from a single center, 1988-2004. Isr Med Assoc J 2007;9:424-9.  Back to cited text no. 13
Bakhshi S, Padmanjali KS, Arya LS. Infections in childhood acute lymphoblastic leukemia: An analysis of 222 febrile neutropenic episodes. Pediatr Hematol Oncol 2008;25:385-92.  Back to cited text no. 14
Ghosh I, Raina V, Kumar L, Sharma A, Bakhshi S, Thulkar S, et al. Profile of infections and outcome in high-risk febrile neutropenia: Experience from a tertiary care cancer center in India. Med Oncol 2012;29:1354-60.  Back to cited text no. 15
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. 16
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El-Mahallawy HA, El-Wakil M, Moneer MM, Shalaby L. Antibiotic resistance is associated with longer bacteremic episodes and worse outcome in febrile neutropenic children with cancer. Pediatr Blood Cancer 2011;57:283-8.  Back to cited text no. 17
Paul M, Lador A, Grozinsky-Glasberg S, Leibovici L. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev 2014;1:CD003344.  Back to cited text no. 18
Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al. 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. Haematologica 2013;98:1826-35.  Back to cited text no. 19


  [Table 1], [Table 2], [Table 3]

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