|Year : 2014 | Volume
| Issue : 4 | Page : 428-431
Invasive bacterial infections in a pediatric oncology unit in a tertiary care center
A Trehan1, S Totadri1, V Gautam2, D Bansal1, P Ray2
1 Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||1-Feb-2016|
Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
Background: Multidrug resistant (MDR) pathogens are becoming a major problem worldwide, more so in the immunocompromised hosts resulting in the urgent need of antibiotic stewardship. Purpose: To analyze the organisms isolated and the drug resistance pattern in a pediatric oncology unit. Results: Data pertaining to infections with 128 positive cultures in patients with febrile neutropenia over a period of 1-year are presented. The unit antibiotic policy is decided depending on the sensitivity of the prevailing common organisms. We isolated Gram-negative organisms in 56% cases. Escherichia coli and Klebseilla were the most frequent lactose fermenting Gram-negative Bacilli and Pseudomonas and Acinetobacter the nonfermenting Gram-negative Bacilli. Only 20–30% of the Gram-negative organisms cultured were sensitive to a 3rd/4th generation cephalosporin. The combination of a beta-lactam/inhibitor covered 2/3rd of Gram-negative organisms. About 80% of the organisms were sensitive to carbapenems. There was no colistin resistance. About 44% of our cultures grew a Gram-positive bacterial organism and included coagulase negative Staphylococcus. We had an incidence of methicillin resistant Staphylococcus aureus to be 30%. About 30% of the enterococci isolated in our unit were vancomycin-resistant enterococci. About 23% of patients with a positive bacterial culture died. Conclusions: Infections in pediatric cancer patient's account for about 15–20% of the deaths in developing countries as these patients are at a high risk for developing MDR infections. Resistance rates among Gram-positive and Gram-negative organisms have increased worldwide. Every unit needs a rational antibiotic policy. Antibiotic de-escalation and judicious decrease in the duration of antibiotics needs to be practiced.
Keywords: Children, culture, febrile neutropenia, sensitivity
|How to cite this article:|
Trehan A, Totadri S, Gautam V, Bansal D, Ray P. Invasive bacterial infections in a pediatric oncology unit in a tertiary care center. Indian J Cancer 2014;51:428-31
|How to cite this URL:|
Trehan A, Totadri S, Gautam V, Bansal D, Ray P. Invasive bacterial infections in a pediatric oncology unit in a tertiary care center. Indian J Cancer [serial online] 2014 [cited 2020 Jan 29];51:428-31. Available from: http://www.indianjcancer.com/text.asp?2014/51/4/428/175368
| » Introduction|| |
Febrile neutropenia (FN) is a recognized complication of therapy in children with malignancies. It remains an important cause of morbidity, in the form of increasing complications, duration of hospital stay and mortality in these patients.,, Worldwide multidrug resistant (MDR) pathogens are becoming a major problem, more so in the immunocompromised hosts. The need for a rational antibiotic policy, the urgent need to prevent the development of MDR organisms and to ensure the well-being of a patient is a balancing task for an oncology unit, needing the collaboration of the oncologist and the microbiologist. Units need to adopt an "escalation" and a "de-escalation policy" while managing patients with FN. A review of local resistance patterns need to be taken up regularly and carefully crafted antibiotic choice is the need of the hour as there are limited available antibiotics available for MDR pathogens. Additionally, identification of factors associated with increased risk of morbidity and mortality can help in the risk stratification and management of these patients.,,
| » Methodology|| |
This was a prospective study carried out over 1-year from March 2013 to February 2014. Data pertaining to infections with positive cultures in patients admitted with FN were entered on a predesigned proforma in the oncology unit. This included the demographics of the patient, site of organism cultured and the susceptibility of the organism. These data are analyzed every year. The antibiotic policy of the unit is changed as per the sensitivity pattern of the prevailing organisms. Predefined descriptions are used to classify various findings, e.g. FN, complications, sepsis etc., (defined below).
All children were on protocol-based treatment for their malignancy. Patients with FN were managed as inpatients based on modified institutional FN guidelines consistent with the recommendations of Infectious Diseases Society of America. Unit antibiotic policy was decided depending on the susceptibility of the prevailing common organisms. All children were evaluated clinically at admission. Hemoglobin, absolute neutrophil count, platelet count, serum electrolytes, serum creatinine, blood urea, C reactive protein and blood culture were sent at admission. Two blood cultures (peripheral and central) were taken in children with permanent central venous catheters. Cultures from other sites (skin lesions, stools, urine) were sent, in the presence of any focal signs and/or symptoms. Chest X-ray was done in the presence of any clinical sign or symptoms suggestive of pneumonia or if the fever persisted beyond 4 days. Broad spectrum antibiotics were started promptly at admission. Cefoperazone-sulbactum and amikacin were the unit protocol for FN to be started empirically upon presentation. Intravenous cloxacillin was added in patients with pneumonia or those with evidence of soft tissue infection. Vancomycin was added at presentation for any of the following: Obvious central venous catheter infection or evidence of septic shock. Second-line antibiotics of a carbapenem and vancomycin were started after 48–72 h of continued fever or earlier if there was any worsening of the clinical condition or hemodynamic instability. In case of culture positivity, antibiotics were changed as per se nsitivity. Blood cultures, complete blood counts were repeated every 48–72 hourly in patients with persistent fever. Empiric antifungal therapy was added if the patient continued to be febrile on day 5–7 of antibiotics and neutropenia was expected to last longer than 5–7 days. Other laboratory, radiological investigations and modification of antibiotics and antifungals during hospital stay were done as per patient's clinical condition.
We used automated blood culture system (BACTEC 9240), and a culture was sent in 2 bottles. The organisms were identified by matrix-assisted laser desorption and ionization – time of flight and sensitivity testing was done using Kirby-Bauer disc diffusion method as per the CLSI guidelines. For vancomycin susceptibility, vancomycin screen agar was used as per CLSI guidelines.
Febrile neutropenia was defined as presence of a single oral/axillary temperature of ≥38.3°C (101°F) or a temperature of ≥38.0°C (100.4°F) for ≥1 h along with absolute neutrophil count <500/mm 3, or <1000/mm 3 with expected decline to <500/mm 3 within the next 2 days. Invasive bacterial infection was considered if one or both of the following criteria were met: (1) Occurrence of bacteremia, defined as one or more blood cultures positive for a bacterial pathogen, and/or (2) a positive bacterial culture obtained from a usually sterile site (indwelling catheter, urine, cerebrospinal fluid).
| » Results|| |
The Pediatric Hematology-Oncology Unit at our Institute has approximately 400 admissions with FN every year. About 20–25% episodes are culture positive. The analysis of 122 positive bacterial cultures from March 2013 to February 2014 is described herein. The diagnosis and site of collection are given in [Table 1]. Organisms isolated are given in [Table 2]. Pus cultures: Totally, 8 patients had positive pus cultures; 6 grew Staphylococcus aureus and one each had Pseudomonas aeruginosa and coagulase negative staphylococcus.
Urine cultures: Totally, 5 patients had a positive urine culture with 3 having Escherichia coli and 1 each of Klebseilla pneumoniae and Enterococcus fecalis.
Line Infections: There were 7 documented line infections. These included K. pneumoniae, P. aeruginosa, coagulase negative Staphylococcus and S. aureus.
We isolated Gram-negative organisms in 56% cases [Table 3]. Among the lactose fermenting Gram-negative Bacilli (LFGNB) isolates, E. coli and K. pneumoniae were the most frequent and in the nonfermenting Gram-negative Bacilli (NFGNB); P. aeruginosa and Acinetobacter baumannii were the most common. Only 20–30% of the Gram-negative organisms cultured were sensitive to a 3rd/4th generation cephalosporins. There was a higher sensitivity to cephalosporins by the NFGNB organisms as compared to the LFGNB. The combination of a beta-lactam/beta-lactamase inhibitor (cefoperazone-sulbactam or piperacillin-tazobactam) covered 2/3rd of the Gram-negative bacterial isolates. About 80% of Gram-negative organisms were sensitive to amikacin, the aminoglycoside in use in our unit, as compared to 54% sensitivity to gentamicin. About 80% of the organisms isolated were sensitive to carbapenems. As per se nsitivity, E. coli and A. baumannii were the 2 organisms that had only 45% sensitivity toward cefoperazone-sulbactam, the first-line antibiotic used in the unit. However, they had a sensitivity of 80% and 60% toward amikacin that we use in combination with cefoperazone-sulbactam as first-line therapy for FN. About 50–75% of the organisms isolated were extended spectrum beta-lactamase (ESBL) producers, pointing toward the need of a carbapenem as the first line antibiotic.
|Table 3: Common Gram-negative isolates in blood and their sensitivity (all figures are %)|
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Forty-four percent of our cultures grew a Gram-positive bacterial organism, the most common organism being coagulase negative Staphylococcus [Table 4]. It's to be noted here that Staphylococcus epidermidis and Staphylococcus hominis were the most common species isolated followed by Staphylococcus haemolyticus. None of these was a contaminant as all grew within 24–48 h of taking the culture and it was isolated from both bottles with the same susceptibility pattern. We had an incidence of methicillin resistant S. aureus (MRSA) to be approximately 30%. All these organisms were sensitive to vancomycin and were 100% susceptible to linezolid, teicoplanin, and netilmicin. About 30% of the Enterococci isolated in our unit were resistant to vancomycin (Vancomycin-resistant enterococci;VRE). About 30% of VRE were also resistant to teicoplanin. All were sensitive to linezolid.
|Table 4: Common Gram-positive isolates in blood and their sensitivity (%)|
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The sensitivity pattern in the oncology unit was similar to the prevailing sensitivity pattern of these organisms in the general pediatric wards of the hospital. The pediatric oncology unit and the general pediatric wards are housed in the same building and are neighboring wards.
There were 29 deaths in the patients who had bacterial septicemia.
Klebsiella pneumoniae (8): Totally, 7 were sensitive to carbapenems, 1 having intermediate sensitivity. Totally, 6 of these were sensitive to amikacin as well as piperacillin-tazobactam.
Enterobacter (2) All sensitive to carbapenems.
E. coli (9): Eight were sensitive and 1 was resistant to carbapenems. Only 3 were sensitive to cephalosporins.
Staphylococcus aureus (2): Both of these were sensitive to vancomycin.
Enterococcus (2): One of these was resistant to vancomycin.
Coagulase negative staphylococcus (2): Both were sensitive to vancomycin. However, one patient was resistant to clindamycin, erythromycin, and ciprofloxacin.
Stenotrophomonas maltophilia (1): This organism was sensitive only to cotrimoxazole.
Acinetobacter baumannii (3): All these 3 were resistant to cephalosporins and only 2 were sensitive to carbapenems.
The sensitivity pattern of the organisms in patients who died was similar to the overall sensitivity pattern reported in the unit.
| » Discussion|| |
Infections in pediatric cancer patients account for about 3% of the deaths in the developed world.,, In developing countries, the figure is higher with reports ranging from 15% to 20%. In our oncology unit, we have treatment-related mortality of 15% attributable to infection.
Most oncology centers use initial therapy with a 3rd generation cephalosporin or piperacillin-tazobactam combination with or without an aminoglycoside.,, This may be inadequate or result in increased mortality keeping in view the resistant organisms., Secondly, in Gram-positive infections, a high MRSA rate results in the use of vancomycin that may result in the emergence of staphylococci with raised vancomycin MICs.
In India, MRSA is at present endemic with rates varying between 25% to 50% across the country. Community-acquired MRSA has also been described. There is a higher incidence of MRSA in intensive care units and hospitals as compared to outpatients. The incidence of MRSA in our Institute is 36%. In Gram-negative infections, the production of ESBLs is the most important mechanism of resistance to third generation cephalosporins. In India, the reported occurrence of ESBL producers resulting in resistance to third generation cephalosporins is around 70%., An increase in the occurrence of ESBLs has been seen. In addition, ESBL production is higher in E. coli and K. pneumoniae as compared to NFGNB. NFGNBs are opportunistic organisms and have shown to have intrinsic resistance to antibiotics posing a challenge to the clinician and the microbiologist. These organisms are being seen to be resistant to commonly used antibiotics. In our analysis, P. aeruginosa had a good sensitivity to conventional antibiotics while Acinetobacter had a sensitivity of only 30–50% to cephalosporins, β-lactam/β-lactamase inhibitor combinations. Reports from units across India give results of resistance to cephalosporins to LFGNB to be around 50% and a higher resistance of 60–70% in NFGNB.,,,, Additionally, development of resistance to carbapenems has become a matter of concern with sensitivity to carbapenems being around 80–90% in most Gram-negative organisms.,,,
In the current scenario, an antibiotic de-escalation approach is required. This would include initial de-escalation to a narrower spectrum once an organism has been identified. In addition, units need to consider avoiding/stopping the use of newer antibiotics toward which resistance has not been reported, when an organism has not been isolated. Switching to oral therapy in a low-risk neutropenic patient in a hospital setting is another method of de-escalation.,,
Traditional teaching advocated administration of antibiotics until neutrophil recovery. Literature abounds with information on the duration of antibiotics in FN. In our hospital, we stop parenteral antibiotics in patients who are "low risk," which includes being afebrile for 24 h, negative blood culture, and a well-looking child. Most recent studies and guidelines advocate an early discharge and a decrease in the duration of parenteral antibiotics.,, Relapse of FN has been seen to occur, but this is seen to be independent of early discontinuation of antibiotics. In case of a documented infection, antibiotics may be continued for a period of 7–10 days. De-escalation and early stoppage of therapy are also important to prevent MDR pathogens and also avoid susceptibility to fungi and Clostridium difficile infections.
Drug-resistant pathogens are a major problem to health care providers worldwide. Drug resistance is seen in the community as well as in hospital-acquired organisms. Drug resistance results in a longer duration of treatment, an increased cost toward health care as also a higher mortality. Patients being treated in a hematology oncology unit are at a high risk for developing MDR infections. The main reasons for this include repeated hospitalization and exposure to broad spectrum antibiotics (especially cephalosporins), and the possibility of past nosocomial infections. Use of prophylactic antibiotics also increases the risk of resistant pathogens. Resistance rates among Gram-positive and Gram-negative organisms have increased worldwide and vary in different hospitals and units. Every hospital and unit have to design an empirical antibiotic protocol based on the resistant pattern seen in their hospital., In addition, one has to minimize the empirical use of newer antibiotics to prevent the development of resistance.
Concluding, we need to develop antibiotic stewardship in all units across the country and ensure a rational antibiotic policy that is reviewed at regular intervals. De-escalation of therapy needs to be practiced. Lastly, infection control needs to be the priority of every health care personnel.
| » References|| |
Santolaya ME, Alvarez AM, Avilés CL, Becker A, Mosso C, O'Ryan M, et al.
Admission clinical and laboratory factors associated with death in children with cancer during a febrile neutropenic episode. Pediatr Infect Dis J 2007;26:794-8.
Bakhshi S, Padmanjali KS, Arya LS. Infections in childhood lymphoblastic leukemia: An analysis of 222 febrile neutropenic episodes. Pediatr Hematol Oncol 2008;25:385-92.
Kanafani ZA, Dakdouki GK, El-Chammas KI, Eid S, Araj GF, Kanj SS. Bloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon: A view of the past decade. Int J Infect Dis 2007;11:450-3.
Klaassen RJ, Goodman TR, Pham B, Doyle JJ. "Low-risk" prediction rule for pediatric oncology patients presenting with fever and neutropenia. J Clin Oncol 2000;18:1012-9.
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.
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al.
Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Disease Society of America. Clin Infect Dis 2011;52:e56-93.
Clinical Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; 20th
Informational Supplement. Wayne, PA: CLSI Document M100-S20 Clinical Laboratory Standards Institute; 2013.
Basu SK, Fernandez ID, Fisher SG, Asselin BL, Lyman GH. Length of stay and mortality associated with febrile neutropenia among children with cancer. J Clin Oncol 2005;23:7958-66.
Hakim H, Flynn PM, Knapp KM, Srivastava DK, Gaur AH. Etiology and clinical course of febrile neutropenia in children with cancer. J Pediatr Hematol Oncol 2009;31:623-9.
Gyssens IC, Kern WV, Livermore DM, ECIL-4, a Joint Venture of EBMT, EORTC, ICHS and ESGICH of ESCMID. The role of antibiotic stewardship in limiting antibacterial resistance among hematology patients. Haematologica 2013;98:1821-5.
Gudiol C, Tubau F, Calatayud L, Garcia-Vidal C, Cisnal M, Sánchez-Ortega I, et al.
Bacteraemia due to multidrug-resistant Gram-negative Bacilli
in cancer patients: Risk factors, antibiotic therapy and outcomes. J Antimicrob Chemother 2011;66:657-63.
Tumbarello M, Spanu T, Sanguinetti M, Citton R, Montuori E, Leone F, et al.
Bloodstream infections caused by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae
: Risk factors, molecular epidemiology, and clinical outcome. Antimicrob Agents Chemother 2006;50:498-504.
Joshi S, Ray P, Manchanda V, Bajaj J, Chitnis DS, Gautam V, et al
. Methicillin resistant Staphylococcus aureus
(MRSA) in India: Prevalence and susceptibility pattern. Indian J Med Res 2013;137:363-9.
Umadevi S, Kandhakumari G, Joseph NM, Kumar S, Easow JM. Prevalence and antimicrobial susceptibility pattern of ESBL producing gram-negative Bacilli
. J Clin Diagn Res 2011;5:236-9.
Arora S, Gautam V, Ray P. Changing susceptibility patterns of nonfermenting Gram-negative Bacilli
. Indian J Med Microbiol 2012;30:485-6.
Samanta P, Gautam V, Thapar R, Ray P. Emerging resistance of non-fermenting gram negative Bacilli
in a tertiary care centre. Indian J Pathol Microbiol 2011;54:666-7.
Alam MS, Pillai PK, Kapur P, Pillai KK. Resistant patterns of bacteria isolated from bloodstream infections at a university hospital in Delhi. J Pharm Bioallied Sci 2011;3:525-30.
Balan K, Sujitha K, Vijayalakshmi TS. Antibiotic susceptibility pattern of gram-negative clinical isolates in ateaching tertiary care hospital. Sch Appl Med Sci 2013;1:76-9.
Gopalakrishnan R, Sureshkumar D. Changing trends in antimicrobial susceptibility and hospital acquired infections over an 8 year period in a tertiary care hospital in relation to introduction of an infection control programme. J Assoc Physicians India 2010;58 Suppl:25-31.
[Table 1], [Table 2], [Table 3], [Table 4]
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