|Year : 2010 | Volume
| Issue : 4 | Page : 391-396
The effect of age on the bacteria isolated and the antibiotic-sensitivity pattern in infections among cancer patients
P Kumar, A Medhekar, NS Ghadyalpatil, V Noronha, S Biswas, P Kurkure, R Nair, R Kelkar, SD Banavali
Tata Memorial Hospital, Mumbai, India
|Date of Web Publication||4-Dec-2010|
Tata Memorial Hospital, Mumbai
Source of Support: None, Conflict of Interest: None
Background: Patients with cancer are predisposed to infections. Antimicrobial patterns and antibiotic sensitivity change with increasing age, making choice of empirical therapy more complicated. Materials and Methods: This single-center study aims to try and assess the influence of age on microbiology and antibiotic sensitivity of organisms causing infection in patients with malignant disease. Results : The five most common bacterial pathogens isolated were Pseudomonas sp (245, 26.2%) > Enterocococcus sp (109, 11.66%) > Staphylococcus aureus (107, 11.44%) > Escherichia coli (106, 11.34%) > Klebsiella sp (99, 10.59%). There was no significant change in the distribution of Gram-positive and Gram-negative bacteria with age. However, there was an increase in the occurrence of the Enterobacteriacea group and a decrease in infections caused by nonlactose fermenters with increasing age. The ESBL production increased from 10.52% (12-19 years) to 24.88% (>50 years) as did oxacillin resistance (from 14.3% to 28.1%) among S. aureus isolates. The activity of most antimicrobial agents decreased with increasing age. The decreasing trend of activity was statistically significant for meropenam (73.3-41.2%) against Pseudomonas sp. and for the activity of the aminoglycosides for Acinetobacter sp (61.1-17.4% for amikacin). Conclusions : This suggests that empirical antibiotic therapy needs to be changed on the basis of the age of the patient. It also appears that combination therapy is essential for the empirical treatment of infections in elderly patients with cancer.
Keywords: Cancer, opportunistic infections, age, antibiotic sensitivity
|How to cite this article:|
Kumar P, Medhekar A, Ghadyalpatil N S, Noronha V, Biswas S, Kurkure P, Nair R, Kelkar R, Banavali S D. 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
|How to cite this URL:|
Kumar P, Medhekar A, Ghadyalpatil N S, Noronha V, Biswas S, Kurkure P, Nair R, Kelkar R, Banavali S D. The effect of age on the bacteria isolated and the antibiotic-sensitivity pattern in infections among cancer patients. Indian J Cancer [serial online] 2010 [cited 2020 Aug 10];47:391-6. Available from: http://www.indianjcancer.com/text.asp?2010/47/4/391/73574
| » Introduction|| |
Patients with cancer are predisposed to infections. On many occasions, no focus of infection can be established. Thus, there is a need for the use of empirical therapy in these patients. The choice of therapy depends on published guidelines, with added consideration of local, regional and national microbiological data obtained from oncology patients. There is evidence to show that antimicrobial patterns and antibiotic sensitivity change with increasing age., The identification of these factors would help tailor the empirical therapy to best suit the individual affected. This single-center study aims to try and assess the influence of age on microbiology and antibiotic sensitivity of organisms causing infection in patients with malignant disease.
| » Materials and Methods|| |
This is a surveillance study carried out at the Tata Memorial Cancer Hospital and Research Center (TMH) in Mumbai, India. TMH is a tertiary care center dealing with the treatment of cancer patients alone. All the samples sent from admitted patients under the Medical Oncology services of the hospital were analyzed. The unique isolates that were obtained from samples that were consistent with a patient history of an appropriate clinical infection were selected. The bacteria were identified by standard biochemical techniques and the in vitro antibiotic sensitivity pattern of these isolates was determined by the disc diffusion method using CLSI standards. The choice of antibiotic discs used for the isolates was dependent on hospital policy. ESBL production was confirmed by CLSI recommendations using cephalosporin-clavulunate combination disks. A difference of >5 mm between zone diameter of either of the cephalosporin discs and their respective cephalosporin-clavulunate disc was taken to be phenotypic confirmation of ESBL production. We used cefotaxime (30 mg), ceftazidime (30 mg) and ceftazidime/clavulanic acid (30 mg/10 mg) discs for ESBL determination. An analysis of the microbiological spectrum and the antibiotic sensitivity pattern of the bacterial isolates was performed. Antibiotic sensitivity and microbiological profile of infection were divided according to three age groups, i.e. 12-19 years, 20-49 years and 50 years and above. The upper limit of age is low as compared to the western literature as the life expectancy at birth in India is 62 years. 
The isolates were mapped on the WHONET 5.4 software. Chi-square test for trend was used to assess the trend of antimicrobial activity with age. The statistical analysis was performed using SPSS 15.0 for Windows. Two-tailed P-values were reported.
| » Results|| |
A total of 935 isolates were obtained, which indicated infection in cancer patients. The origin of the isolates was the blood stream (51.76%), respiratory tract (15.08%), gastrointestinal tract (12.62%), skin and soft tissue (11.55%), urinary tract (3.32%) and other infection sites (5.67%).
The overall rank order of the most common pathogens was (no. of isolates/% of total) Pseudomonas sp (245, 26.2%) > Enterocococcus sp (109, 11.66%) > S. aureus (107, 11.44%) > E. coli (106, 11.34%) > Klebsiella sp (99, 10.59%) > Acinetobacter sp (93, 9.95%) > Coagulase-negative staphalococcus (CoNS) (61, 6.52%) > Streptococcus sp (32, 3.42%) > Enterobacter sp (29, 3.1%) > Burkholderia sp (22, 2.35%). There were 32 other isolates that were identified to their genera, which accounted for 3.42% of the isolates.
The Gram-negative organisms were the predominant group of bacteria, accounting for 66.96% of the isolates. The occurrence of the top eight pathogens as causative agents of infection among the three age groups of cancer patients (12-19, 20-49, >50 years) is shown in [Table 1]. While the proportion of most isolates remains the same, there is an increase in infections caused by E. coli (8.67-13.17%) and Klebsiella sp (7.51-11.11%) with increasing age. This is associated with a fall in infections caused by Pseudomonas sp (30.01-23.87%) and a minor decrease in CoNS infections (6.94-5.35%) and Acinetobacter sp (10.40-9.47%).
|Table 1: Percentage of occurrence of bacterial pathogens among the three age groups|
Click here to view
ESBL production was identified among 122 isolates. The incidence increased with increasing age, from 10.52% (12-19 years) to 19.31% (20-49 years) to 24.88% (>50 years) among the Gram-negative isolates.
Statistical analysis of the isolation of microorganisms was performed in the three defined age groups. There was no statistically significant difference in these groups in all the microbe distributions except for the ESBLs. ESBL incidence was 6.59% in 12-19 years, 12.36% in 20-49 years and 17.9% in the age group more than 50 years. This difference was statistically significant when each of this age group was compared with the other (P < 0.01).
The antibiotic sensitivity of the eight most common bacterial groups against selected antibiotics is shown in [Table 2] and [Table 3]. The most active antibiotic against the Gram-positive organisms was linezolid and no resistance was documented against it. Among the Enterococcal sp, vancomycin resistance was common (83% overall). However, there was a decrease in frequency with advanced age (83.6-74.1%). Linezolid was universally sensitive against the Enterococcal isolates. Vancomycin, linezolid and teicoplanin were the most active agents against Staphylococcal isolates, and no resistance was documented. There was some resistance among streptococcal species to vancomycin and teicoplanin (in individuals more than 50 years of age). Clindamycin was highly active against Staphylococcal isolates across all age groups (91.7-100%). Oxacillin resistance increased with increasing age among S. aureus isolates (from 14.3 to 28.1%) and among CoNS (from 16.7 to 23.1%). The efficacy of erythromycin and ciprofloxacin was poor against most of the Gram-positive isolates (range, 0-75%). 
|Table 2: Antimicrobial activity of selected broad spectrum antibiotics against four Gram-negative pathogens isolated from three age groups of patients|
Click here to view
|Table 3: Antimicrobial activity of selected broad spectrum antibiotics against four Gram-positive pathogens isolated from three age groups of patients|
Click here to view
The third generation cephalosporins had a poor activity against all the Gram-negative isolates. The activity was worst against E. coli (12.5-26.7%). Although the antipseudomonal cephalosporin, ceftazidime, had a better activity against Pseudomonas sp (48.3-63.5%), its activity against Acinetobacter sp was poorer (13-50%). Among the beta-lactam/beta-lactamase inhibitor combination, cefoperazone-sulbactam had a better activity profile as compared to piperacillin-tazobactam against all the bacterial species. The carbapenams were the most active agents against most groups. However, their activity against the nonlactose fermenters was poorer as compared to the Enterobactereaciae group (13-75% vs. 90.9-100%). Their lower activity among the Pseudomonas sp can be explained by our hospital policy, wherein the carbapenams are tested only if the isolates are resistant to the cephalosporins and the beta-lactam/beta lactamase inhibitor combinations. The activity of ciprofloxacin was variable but, in general, there was a high degree of resistance among isolates. The aminoglycoside, amikacin in particular, was more effective against the Enterobactereaciae group (62.7-76.9%) but had a lower activity against the nonlactose fermenters (17.4-61.1%).
The activity of most antibiotics against the Acinetobacter sp was poor. The aminoglycosides had reasonable activity among the 12-19-year group (61.1-77.8%), but this fell significantly with increasing age (17.4-34.8% for >50-year group). Colistin and polymyxin were the most active agents against the Acinetobacter sp (88.2-100%).
The activity of most antimicrobial agents decreased with increasing age. The decreasing trend of activity was statistically significant for meropenam (73.3-41.2%) against Pseudomonas sp. and for the activity of the aminoglycosides for Acinetobacter sp (61.1-17.4% for amikacin). There was a statistically significant decrease in the activity of gentamicin (53.3-28.1%) and netilmicin (60-43.8%) against E. coli, but the linear decrease in trend could not be established. A similar feature was seen with ceftazidime against Acinetobacter sp (38.5-14.8%). There was a significant decreasing trend of cefoperazone-sulbactam (73.1-53.4%) and imipenam (59.4-32.4%) against Pseudomonas sp, but this did not reach statistical significance. The only exception was the improving efficacy of polymyxin and colistin against Pseudomonas sp (40-91.7%), which was statistically significant. There was also an increase in the activity of teicoplanin against enterococcal species with increasing age (31.8-42.3%), although this did not reach statistical significance.
| » Discussion|| |
Infections cause significant morbidity and mortality in cancer patients. Broad spectrum antibiotics are commonly used as empirical therapy in febrile cancer patients. The use of "early empirical" therapy has reduced the mortality in patients with leukemia and bacteremia from 85% to 20-36% over the last five decades.  However, the widespread use of antimicrobials has resulted in the emergence of multidrug-resistant bacteria. It is essential therefore to monitor trends of antimicrobial resistance and develop appropriate antibiotic policy.
This study reveals that the most predominant causative organisms among cancer patients are Gram-negative bacteria. This is in contrast to the findings in developed countries, , but is in keeping with similar studies from developing countries that have reported this occurrence.,, The reasons for this include the decreased use of intravascular catheters and the low utilization of antimicrobial prophylaxis in these geographic areas. The greater emphasis of broad spectrum empirical therapy on the treatment of Gram-negative infections should theoretically benefit developing countries to a greater extent. However, it also predisposes to the selection of multidrug-resistant organisms,  a fact that was borne out amply in this study.
The contribution of Gram-positive and Gram-negative organisms remains fairly constant with increasing age. This is unlike similar studies that showed an increase in Gram-negative infections.  There is, however, an increase in infections due to the Enterobacteriacae group of organisms and a decline in infections caused by CoNS, a fact evident in similar studies.  The large proportion of nonlactose fermenters as cause of infection, evident in our study, has not been reported elsewhere to the best of our knowledge. The high incidence combined with the extensive antibiotic resistance of Acinetobacter sp and Pseudomonas sp is distressing.
The increased incidence of methicillin-resistant S. aureus among the elderly should be viewed seriously and consideration for vancomycin therapy at an early stage might be prudent.  However, teicoplanin was more effective against Enterococcal isolates among the elderly in this study. This might prompt the use of teicoplanin over vancomycin as the choice of empirical therapy for Gram-positive organisms in the elderly.
There is an evident trend of decreasing antibiotic sensitivity with increasing age.  Studies have shown decreasing efficacy of quinolones for Streptococcus pnemoniae in the elderly.  But, this study demonstrates that efficacy of most antibiotics decreases with age. There is a statistically significant declining trend for aminoglycosides against Acinetobacter sp and that of cefoperazone-sulbactam, imipenam and meropenam against Pseudomonas sp. With increasing age, lower proportions of isolates are sensitive to the majority of antibiotics. The reasons for this could be greater exposure to antibiotics during life, associated comorbidities, higher ESBL production and need for more invasive procedures. This suggests that empirical antibiotic therapy needs to be changed on the basis of the age of the patient. It also appears that combination therapy is essential for the empirical treatment of infections in elderly patients with cancer.
Among the antibiotics suggested by the Infectious Disease Society of America for empirical therapy in neutropenic patients,  only the carbapenams have reasonable sensitivity among the elderly patients. Consideration should be given to the use of these agents as the only antibiotics for empirical therapy in elderly patients with cancer. This approach might lead to widespread development of resistance against this group of antibiotics, highlighting the grave situation among elderly patients with cancer. There is thus an emergent need for the development of novel agents for the treatment of Gram-negative infections. However, this has to be combined with sound infection control practices and responsible antibiotic use.
| » References|| |
|1.||Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, et al. Harrison's principles of internal medicine. 17th ed. vol 1 New York (NY): McGraw Hill Medical; 2008. p. 533. |
|2.||Jones RN, Biedenbach DJ, Beach ML. Influence of patient age on the susceptibility patterns of Streptococcus pneumoniae isolates in North America (2000-2001): report from the SENTRY Antimicrobial Surveillance Program. Diagn Microbiol Infect Dis 2003;46:77-80. |
|3.||Kirby JT, Fritsche TR, Jones RN. Influence of 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). Diadn Microbiol Infect Dis 2006;56:75-82. |
|4.||Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002;34:760-51. |
|5.||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. |
|6.||Gonzαlez-Barca E, Fernαndez-Sevilla A, Carratalα J, Graρena A, Gudiol F. Prospective study of 288 episodes of bacteremia in neutropenic cancer patients in a single institution. Eur J Clin Microbiol Infect Dis 1996;15:291-6. |
|7.||Figuera Esparza M, Carballo M, Silva M, Figueredo A, Avilαn J. Microbiological isolates in patients with febrile neutropenia and hematological neoplasias [Article in Spanish]. Rev Esp Quimioter 2006;19:247-51. |
|8.||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. |
|9.||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. |
|10.||Jones RN. Contemporary antimicrobial susceptibility patterns of bacterial pathogens commonly associated with febrile patients with neutropenia. Clin Infect Dis 1999;29:495-502. |
|11.||Registrar General of India (2003) SRS Based Abridged Life Tables, SRS Analytical Studies, Report No. 3 of 2003, New Delhi: Registrar General of India. |
|12.||Feld R. Bloodstream infections in cancer patients with febrile neutropenia. Int J Antimicrob Agents 2008;32:S30-3. |
|13.||Velasco E, Byington R, Martins CS, Schirmer M, Dias LC, Gonηalves VM. Bloodstream infection surveillance in a cancer centre: a prospective look at clinical microbiology aspects. Clin Microbiol Infect 2004;10:542-9. |
|14.||Diekema DJ, Pfaller MA, Jones RN; SENTRY Participants Group. Age-related trends in pathogen frequency and antimicrobial susceptibility of bloodstream isolates in North America: SENTRY Antimicrobial Surveillance Program, 1997-2000. Int J Antimicrob Agents 2002;20:412-8. |
[Table 1], [Table 2], [Table 3]
|This article has been cited by|
||Bacteremia in febrile cancer patients in Uganda
| ||Margaret Lubwama,Warren Phipps,Christine F. Najjuka,Henry Kajumbula,Henry Ddungu,Joyce B. Kambugu,Freddie Bwanga |
| ||BMC Research Notes. 2019; 12(1) |
|[Pubmed] | [DOI]|
|| result 1 Document Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer: Current epidemiology and clinical impact
| || Trecarichi, E.M., Tumbarello, M. |
| ||Source of the Document Current Opinion in Infectious Diseases. 2014; |
||Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer
| ||Enrico M. Trecarichi,Mario Tumbarello |
| ||Current Opinion in Infectious Diseases. 2014; 27(2): 200 |
|[Pubmed] | [DOI]|