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ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 4  |  Page : 496-501
 

Comparison of isolates and antibiotic sensitivity pattern in pediatric and adult cancer patients; is it different?


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

Date of Web Publication1-Feb-2016

Correspondence Address:
J Bajpai
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.175356

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 » Abstract 

Background: Infection is a common cause of mortality and morbidity in cancer patients. Organisms are becoming resistant to antibiotics; age appears to be one of the factors responsible. We analyzed common organisms and their antibiotic sensitivity pattern in the correlation with age. Methods: This is a single institutional, retrospective analysis of all culture positive adult and pediatric cancer patients from January 2007 to December 2007. For statistical analysis, Chi-square test for trend was used and P values were obtained. Of 1251 isolates, 262 were from children <12 years of age and 989 were from adolescents and adults (>12 years of age). Gram-negative organisms were predominant (64.95) while Gram-positive constituted 35.09% of isolates. Results: The most common source in all age groups was peripheral-blood, accounting to 47.8% of all samples. The most common organisms in adults were Pseudomonas aeruginosa (15.3%) while in children it was coagulase negative Staphylococcus aureus (19.8%). Antibiotic sensitivity was different in both groups. In pediatric group higher sensitivity was seen for Cefoparazone-sulbactum, Cefipime, Amikacin, and Tobramycin. No resistance was found for Linezolid. Conclusions: The isolates in both children and adults were predominantly Gram-negative though children had proportionately higher Gram-positive organisms. High-dose cytarabine use, cotrimoxazole prophylaxis, and frequent use of central lines in children especially in hematological malignancies could explain this observation. Children harbor less antibiotic resistance than adults; Uncontrolled, cumulative exposure to antibiotics in our community with increasing age, age-related immune factors and variable bacterial flora in different wards might explain the higher antibiotic resistance in adults. Thus age is an important factor to be considered while deciding empirical antibiotic therapy.


Keywords: Age trends, antibiotic resistance, malignancy


How to cite this article:
Prabhash K, Bajpai J, Gokarn A, Arora B, Kurkure P A, Medhekar A, Kelkar R, Biswas S, Gupta S, Naronha V, Shetty N, Goyel G, Banavali S D. Comparison of isolates and antibiotic sensitivity pattern in pediatric and adult cancer patients; is it different?. Indian J Cancer 2014;51:496-501

How to cite this URL:
Prabhash K, Bajpai J, Gokarn A, Arora B, Kurkure P A, Medhekar A, Kelkar R, Biswas S, Gupta S, Naronha V, Shetty N, Goyel G, Banavali S D. Comparison of isolates and antibiotic sensitivity pattern in pediatric and adult cancer patients; is it different?. Indian J Cancer [serial online] 2014 [cited 2019 Dec 14];51:496-501. Available from: http://www.indianjcancer.com/text.asp?2014/51/4/496/175356



 » Introduction Top


Infection is a common cause of mortality and morbidity in cancer patients. Repeated hospitalizations, presence of neutropenia, use of antibiotics and intravenous (IV) catheters make these patients prone to infections with drug-resistant organisms. Initial therapy is almost always empirical. The choice of antibiotics must be guided by published guidelines and local, regional and national microbiological data.[1] Many times in the absence of focus of infection and failure to grow microorganism in culture, antibiotics have to be continued empirically.

Age of patient is a factor known to influence not only the occurrence, but also the sensitivity patterns of organisms causing infections.[2],[3],[4] However, most of this data is from the western world. Most centers in the developing world do not have such robust surveillance data to guide choice of antibiotics. Availability of such data can help in the choice of initial antibiotic selection in patients, thus minimizing the selection of resistant strains. Targeting therapies using the influence of patient age can help prudent usage of antimicrobials and reduce the emergence of resistant organisms.

Therefore, we tried to analyze common organisms and their antibiotic sensitivity patterns in relation to age of the patient. This information should be useful for clinicians when they prescribe empirical antibiotics for cancer patients with suspected infections across the age continuum. In this article we present age-related trends in pathogen frequency and antimicrobial susceptibility.


 » Methods Top


This is a single institutional, retrospective analysis of all culture positive adult and pediatric cancer patients from January 2007 to December 2007, carried out at Tata Memorial Centre, (Mumbai) which is a tertiary institute for treatment of cancer patients. This hospital offers a holistic oncology care (including surgical oncology, radiation oncology, medical oncology and palliative care services) to patients. Many cancer patients are either admitted with infections or develop infections during course of admission, and require testing of various body fluids (blood, urine, sputum, bronchoalveolar lavage, pus discharge, pleural fluid etc.) for presence of bacterial organisms. The decision of when to order such an investigation is at the discretion of treating physician. Sometimes these tests are done on outpatient basis. We analyzed all positive cultures between January 2007 to December 2007 that were sent from patients from medical oncology department. The isolates that were obtained from samples and were consistent with a clinical setting of an infection were selected. Data was captured regarding the age of patient, type of fluid sent, the organisms grown and their respective sensitivity pattern. The samples were collected using standard procedures and by following general principles of sample collections.[5],[6] The samples collected were processed in the microbiology department at our center. Standard biochemical tests were used for bacterial identification and disc diffusion method was then used to determine the antibiotic sensitivity pattern. The choice of antibiotic discs being used for sensitivity testing was based on hospital policy. The antibiotic discs were procured from CLSI approved centers.

For the analysis of data patients were divided into age groups of <12 years, 12–19 years, 20–49 years and >50 years.

Statistical methods

WHONET 5.4 software, (WHO Collaborating Centre for Surveillance of Antimicrobial Resistance, Boston, MA, USA.) was used for mapping isolates. We used Chi-square test for trend to determine correlation between age and antibiotic sensitivity pattern. SPSS version 15.0 software (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. P values were calculated for antibiotics which showed a trend across age groups. P value was calculated using Chi-square test.


 » Results Top


In total 1251 organisms were isolated in total, of which 262 were in children <12 years of age and 989 were in adolescents and adults (>12 years of age). Gram-negative (812/64.9%) were the predominant organisms grown across all age groups, while Gram-positive represented 35.09% (439) of isolates. However, the proportion of Gram-positive organisms was more in children (45.8%) when compared to adults (32.6%).

The most common source in adults and adolescents as well as in children was peripheral-blood, accounting to 47.8% of all samples. IV catheters (11.5%), respiratory (sputum - 11% and bronchoalveolar lavage - 4%), skin and soft tissue (11%) were other frequent sites of infections. Urinary infections represented only 3% of isolates. Pus, catheter tips, wound swabs, stool, cerebrospinal fluid accounted for remaining 11.7% of isolated organisms.

The important organisms grown in respective age groups are shown in [Table 1].
Table 1: Percentage of occurrences of bacterial pathogens in the four age groups

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The most common organism in adults and adolescents was Pseudomonas aeruginosa (15.3%) while in children <12 years it was coagulase negative staphylococcus (CoNS) (19.84%), followed closely by Staphylococcus aureus (S. aureus) (18.32%). In patients >12 years S. aureus and CoNS accounted for 11.4 and 6.16%, respectively. Overall, across all age groups, P. aeruginosa (178/14.2%) was the most common species isolated, followed by other Pseudomonas species (165/13.1%) and S. aureus (160/12.7%). Other organisms grown in decreasing order of frequency include acinitobacter species (128/10.2) Escherichia coli (128/10.2), Enterococcus (119/9.51%), CoNS (113/9.03%), and Klebsiella (111/8.87). Gram-positive organisms, especially CoNS was more common in children and was progressively less frequent in higher age groups. While in contrast in Gram-negative organisms, E. coli and Klebsiella there was a progressively increasing trend in higher age groups. Isolates that were less frequently grown were Streptococcus pneumoniae, and among the Gram-negative organisms – Enterobacter cloacae, Salmonella, Klebsiella oxytoca and Proteus mirabilis. Few (11) isolates of Shewanella putrefaciens and of Citrobacter were found in wound swabs. 5 isoloates of Burkholderia sp. were seen, all were in age groups >12 years of age. The total number of Stenotrophomonas maltophilia across the age groups were 6.

The age-related trends of 4 most common Gram-negative and Gram-positive organisms is shown in [Figure 1] and [Figure 2].
Figure 1: Percent of all pathogens in cancer patients (January – December 1997). Four most common Gram-positive pathogens, by age. Total n = 1251; <12 years = 262; 12–19 years = 182, 20–49 years = 550; >50 years = 257

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Figure 2: Percent of all pathogens in cancer patients (January – December 1997). Four most common Gram-negative pathogens, by age. Total n = 1251; <12 years = 262; 12–19 years = 182, 20–49 years = 550; >50 years = 257

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Antibiotic sensitivity pattern was different in children <12 years compared to others. The sensitivity patterns of 4 most common Gram-negative and Gram-positive organisms are summarized in [Table 2] and [Table 3] respectively.
Table 2: Antibiotic activity of selected broad spectrum antibiotic against four Gram--negative organisms according to four age groups

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Table 3: Susceptibility pattern of four Gram--positive organisms for selected broad spectrum antibiotics, according to different age groups

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The isolates of Klebsiella and Pseudomonas were more sensitive to cephalosporins, ceftazidime and cefoperazone-sulbactum in children and adolescent age groups compared to higher age groups, which was statistically significant. Similarly, sensitivity of Klebsiella and Pseudomonas to amikacin decreased significantly with age. Furthermore, there was increasing resistance of Pseudomonas species to Piperacillin Tazobactam as age increased. The sensitivity of E. coli to carbapenems increased from 89% in children to 100% in patients >50 years. Although statistically of borderline significance, the increment was rather small. In general, E. coli species isolated across all age groups were sensitive (93% susceptible) to Carbapenems, but were resistant to fluroquinolones (19% susceptible). The resistance of Acinetobacter species to carbapenems and polymixins across all age groups was high.

Most Gram-positive organisms were uniformly sensitive to linezolid, vancomycin and teicoplanin across all age groups, except enterococcal sp. which showed resistance to vancomycin and teicoplanin. About 50% of enterococcal species isolated in children <12 years were susceptible to vancomycin, whereas in adolescents and adults the sensitivity was only 16.8%. Susceptibility of S. aureus to clindamycin and oxacillin was high but resistance to ciprofloxacin was observed in majority of isolates, however CoNS grown were moderately sensitive to ciprofloxacin. The proportion of Methicillin resistant S. aureus increased progressively from 16.7% in children <12 years to 31.3% in adults >50 years.


 » Discussion Top


Although there has been a reduction in mortality and morbidity in cancer patients due to wide spread use of broad spectrum antibiotics, this is being balanced by rapid emergence of multidrug resistant strains of organisms in last few decades.[7] Choosing empiric antimicrobial agents for cancer patients with coexisting bacterial infections is a complex challenge. It is vital to choose appropriate antibiotic so as to prevent selection of resistant strains, while at the same time adequately cover a broad spectrum of possible bacterial pathogens.

Introduction of IV catheters and central lines changed the epidemiology of infections in cancer patients. Gram-positive infections, which are frequently associated with these IV devices, became predominant.[8] Use of fluroquinolones for prophylaxis in severely neutropenic patients (<100 neutrophils/mm 3) have increased the threat of selection of resistant Gram-negative organism.[9]

Monitoring of epidemiologic shifts in the microbial infections and emerging drug resistance within cancer treatment centers using surveillance mechanisms is essential in guiding treatment. Age related trends of infections and their antibiotic resistance patterns, amongst cancer patients can help in optimizing the therapeutic options by identification of pathogens predominantly seen in particular age group. The study demonstrates an age-related difference in pathogen occurrence, and antimicrobial susceptibility patterns among organisms causing infections in cancer patients. We did not determine whether the organisms isolated were community acquired or nosocomial, hence the isolates probably included community acquired as well as nosocomial organisms.

Gram-negative isolates were found to be more common cause of infections in both adults and children. This is in contrast to data from Western countries where Gram-positive infections were predominant.[8],[10],[11],[12] Trend similar to our data is seen in other developing countries.[13],[14] The reasons for this could be the lower use of intravascular catheters and antimicrobial prophylaxis when compared to western world.[15] Also increasing emphasis on ambulatory care and day care administration of chemotherapy, rather than hospitalization may be a reason for lower proportion of Gram-positive infections.

The most common source in adult and in children (47.8%) was peripheral-blood. This is in keeping with other similar studies.[16]

Although Gram-negative organisms were predominant, the proportion of Gram-positive organisms was comparatively higher in children, compared with adults. The most common organisms in adults were P. aeruginosa (15.3%) while in children it was CoNS (19.8%), followed by S. aureus (18.3%). The significance of high incidence of CoNS in children is not known. High dose cytarabine use and cotrimoxazole prophylaxis could be a reason for this. High incidence of CoNS could also represent contamination of IV catheters and central lines by commensals.

A similar high incidence of CoNS in children has been seen in North American studies.[17] It has been suggested that cross transmission of endemic CoNS strains may be responsible for high incidence in children.[18] In our study, the isolates of CoNS in children were sensitive to vancomycin and linezolid (100%), similar to western data in cancer study (99.8%).[4]

Oxacillin sensitivity of S. aureus was higher in children and adolescents and decreased in higher age groups. The reason for this could be increased exposure to antibiotics and more contact with health care system leading to infection with resistant organisms. This trend of decreasing oxacillin sensitivity is seen in other studies also.[2],[16] Considering neutropenic status of most patients and the above resistance pattern, vancomycin/linezolid may be used upfront in children and must be used in older age groups if Staphylococcal infection is suspected.

Amongst the enterococcal isolates, vancomycin resistance was very high (83.8%) in adults and adolescents, while it was 50% in children <12 years, probably due to the same reasons. Linezolid must be the drug of choice in enterococcal infections, as the isolates were uniformly sensitive to this antibiotic across all ages.

There was a higher proportion of Gram-negative organisms in older age groups as compared with children <12 years, whereas Gram-positive bacteria such as staphylococci and streptococci decreased in higher age groups. Among the E. coli isolates in the children sensitivity to amikacin was higher. Carbapenems were uniformly effective against E. coli in all age groups.

The acinitobacter isolates were relatively resistant to most antibiotics, and were susceptible to only to polymixins. This should be a cause for concern.

Another cause of concern is high resistance of most Gram-negative organisms to fluoroquinolones across all age groups. The isolates were tested for sensitivity to ciprofloxacin, levofloxacin and norfloxacin. This high resistance to fluroquinolones in India has also been seen in a large community-based WHO surveillance project.[19] Currently Infectious Diseases Society of America recommends that fluoroquinolones be used as prophyaxis against bacterial infections in neutropenic patients.[9] In presence of high level of quinolone resistance in India, the effectiveness of such prophylactic regimen needs to be questioned.

In general, the antibiotic resistance among the isolates in India is higher as compared to western countries, a fact which is evident in our study as well. This high resistance has been variously attributed to indiscriminate antibiotic use in community, usage of antibiotics in animals especially poultry and livestock and even to traces of antibiotics being found in food.[20]

The sensitivity to cephalosporins, beta lactam/beta lactamases was higher in children as compared to adults, while that of carbapenems was equal. Hence adult patients, especially older age group could benefit from empirical use of carbapenems more than children, in whom cephalosporins/betalactam-betalactamase combination would be adequate, except when E. coli is suspected organism in which case a combination of amikacin with cephalosporins may be used.

The age related trends in susceptibility were more prominent in Gram-negative than Gram-positive organisms (where it was seen only with oxacillin sensitivity of S. aureus).

In summary, we conclude that there are important age-related differences in pathogen frequency and antimicrobial susceptibility amongst organisms causing infections in our hospital.

The antibiotic resistance among higher age groups is more, as compared to lower age groups. This probably is due to increasing antibiotic exposure and consequent drug resistance. This was statistically significant especially in amikacin and cephalosporin susceptibility of Gram-negative organisms. The Gram-negative organisms were uniformly susceptible to carbapenems (except for acinetobacter and Pseudomonas), however the resistance to other drugs especially fluroquinolones were high. The Gram-positive organisms were uniformly sensitive to linezolid, across all age groups.

Results from this study provide important information regarding differences in pathogen trends, the burden of resistance and antimicrobial susceptibility patterns among children and adults. With newer drug resistence mechanisms like NDM1 emerging,[21],[22] in developing countries it is important to use antibiotics judiciously, and have robust surveillance data to guide antibiotic use.

It may prove useful in emphasizing that in addition to development of new antimicrobial agents, more aggressive approaches to prevention and control of Gram-positive infections-to include infection control measures, vaccine development and most importantly antimicrobial usage regulation-are urgently needed.

 
 » References Top

1.
WHO Workshop on the Containment of Antimicrobial Reisistance in Europe: Report on a WHO Meeting, Wernigerode, Germany; 26-27 February, 2004. Available from: http://www.who.int/drugresistance/infosharing/AMR_WS_WERNIGERODE_REPORT_EURO.pdf. [Last accessed on 2011 Nov 12].  Back to cited text no. 1
    
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Jones RN. Contemporary antimicrobial susceptibility patterns of bacterial pathogens commonly associated with febrile patients with neutropenia. Clin Infect Dis 1999;29:495-502.  Back to cited text no. 7
    
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Feld R. Vancomycin as part of initial empirical antibiotic therapy for febrile neutropenia in patients with cancer: Pros and cons. Clin Infect Dis 1999;29:503-7.  Back to cited text no. 8
    
9.
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 Diseases Society of America. Clin Infect Dis 2011;52:E56-93.  Back to cited text no. 9
    
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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. 12
    
13.
Latiff Z, Zulkifli SZ, Jamal R. Risk assessment and microbiological profile of infections in paediatric cancer patients with febrile neutropenia. Malays J Pathol 2002;24:83-9.  Back to cited text no. 13
    
14.
Butt T, Afzal RK, Ahmad RN, Salman M, Mahmood A, Anwar M. Bloodstream infections in febrile neutropenic patients: Bacterial spectrum and antimicrobial susceptibility pattern. J Ayub Med Coll Abbottabad 2004;16:18-22.  Back to cited text no. 14
    
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Chen CY, Tang JL, Hsueh PR, Yao M, Huang SY, Chen YC, et al. Trends and antimicrobial resistance of pathogens causing bloodstream infections among febrile neutropenic adults with hematological malignancy. J Formos Med Assoc 2004;103:526-32.  Back to cited text no. 15
    
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Kumar P, Medhekar A, Ghadyalpatil NS, Noronha V, Biswas S, Kurkure P, et al. The effect of age on the bacteria isolated and the antibiotic-sensitivity pattern in infections among cancer patients. Indian J Cancer 2010;47:391-6.  Back to cited text no. 16
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Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in pediatric intensive care units in the United States. National Nosocomial Infections Surveillance System. Pediatrics 1999;103:E39.  Back to cited text no. 17
    
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Villari P, Sarnataro C, Iacuzio L. Molecular epidemiology of Staphylococcus epidermidis in a neonatal intensive care unit over a three-year period. J Clin Microbiol 2000;38:1740-6.  Back to cited text no. 18
    
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Holloway K, Mathai E, Sorensen TL, Gray A. (US Agency for International Development). Community-based surveillance of antimicrobial. Use and resistance in resource-constrained settings. Report on five pilot projects. Geneva: World Health Organization; 2009.  Back to cited text no. 19
    
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Ganguly NK, Arora NK, Chandy SJ, Fairoze MN, Gill JP, Gupta U, et al. Rationalizing antibiotic use to limit antibiotic resistance in India. Indian J Med Res 2011;134:281-94.  Back to cited text no. 20
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Sartor a AL, Raza MW, Abbasi SA, Day KM et al. Molecular Epidemiology of NDM-1-ProducingEnterobacteriaceae and Acinetobacter baumannii Isolates from Pakistan. Antimicrob. Agents Chemother. September 2014 vol. 58 no. 95589-5593  Back to cited text no. 21
    
22.
Diep TT, Nguyen NTN, Nguyen TNC, An HK, Nguyen TQ, Nguyen VH, et al. Isolation of New Delhi metallo-β-lactamase 1 (NDM-1)-producing Vibrio cholerae non-O1, non-O139 strain carrying ctxA, st, and hly genes in southern Vietnam. Microbiology and immunology. 2015  Back to cited text no. 22
    


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