Background: Empiric broad-spectrum antibiotic therapy has been the cornerstone of the management of fever in patients with chemotherapy-induced neutropenia. In the face of emerging multidrug-resistant organisms, antimicrobial prophylaxis and treatment have become increasingly difficult in these highly compromised patients. Thus, the local data of common pathogens is important to initiate the appropriate empirical antibiotic therapy.

Objectives: To determine the antimicrobial susceptibility pattern of the blood stream infection isolates in neutropenic patients receiving chemotherapy for solid tumours.

Methods: Antimicrobial susceptibility testing was performed by Kirby-Bauer disc diffusion method on Mueller-Hinton agar as per Clinical Laboratory Standards Institute (CLSI) guidelines. Antibiotic discs were procured from Himedia, Mumbai. The diameters of zones of inhibition were interpreted according to CLSI standards for each organism. Culture media and antibiotic discs were tested for quality control using standard ATCC strains.

Result: Antimicrobial susceptibility testing was done as per CLSI guidelines. The Gram positive isolates showed 100% susceptibility to Vancomycin. Methicillin resistance was seen among 24% of Staphylococcus epidermidis isolates. Staphylococcus aureus isolates were uniformly susceptible to Methicillin. All the Gram negative isolates were found to be ESBL producers by ESBL phenotypic confirmatory double disc test.

Conclusion: The findings highlight the role of Staphylococcus epidermidis, which is commonly considered as a commensal, as a potential pathogen in neutropenic patients, and necessitate the inclusion of antimicrobials having gram positive coverage in the empirical antimicrobial therapy.

Keywords: Neutropenia, Chemotherapy, Blood stream infection, Solid malignancy, Antimicrobial susceptibility.

1.      Pizzo PA. Management of Fever in Patients with Cancer and Treatment-induced Neutropenia. N Engl J Med. 1993;328:1323–32.

2.      National Cancer Institute. Common toxicity criteria, version 2.0. Available from URL: http://ctep.cancer.gov/forms/CTCv20_4-30-992.pdf [access date January 3, 2003].

3.      Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR. Infectious Diseases Society of America (2011) 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: 427–431.

4.      Klastersky J. Management of fever in neutropenic patients with different risks of complications. Clin Infect Dis. 2004; 39: S327.

5.      Montassier E, Batard E, Gastinne T, Potel G, de la Cochetiere MF. Recent changes in bacteraemia in patients with cancer: a systematic review of epidemiology and antibiotic resistance. Eur J Clin Microbiol Infect Dis. 2013; 32: 841–850.

6.      Bodey GP, Buckley M, Sathe YS,  Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia Ann Intern Med 1966; 64: 328-39.

7.      Anatoliotaki M, Valatas V, Mantadakis E, Apostolakou H, Mavroudis D, Georgoulias V, Rolston KV, Kontoyiannis DP, Galanakis E, Samonis G. Bloodstream infections in patients with solid tumors: associated factors, microbial spectrum and outcome. Infection. 2004; 32: 65–71.

8.      Schelenz S, Nwaka D, Hunter PR. Longitudinal surveillance of bacteraemia in haematology and oncology patients at a UK cancer centre and the impact of ciprofloxacin use on antimicrobial resistance. J Antimicrob Chemother. 2013; 68: 1431–1438.

9. Betty A.Forbes, Daniel. F. Sahm, Alice S. Weissfeld Bailey & Scott’s Diagnostic Microbiology 12^th
10. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial disk susceptibility tests. Approved standard, 9 ed. Document M2­A9. Wayne, PA: CLSI; 2006.
11. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. M100-S25.Table 2A,2B-1,2B-2.Jan 2015.35No.3.
12. Screening and confirmatory test for ESBL’s in Enterobacteriaceae isolates. CLSI document M100-S25.Table 3A.Jan 2015.Vol.35No.3.
13. Workshop manual – Antimicrobial susceptibility testing methods. Dept of Microbiology, JSS Medical College and Hospital, Mysore,India.
14. Singhal et al. Evaluation of methods for AmpC beta lactamases in gram negative isolates from tertiary care hospitals. Indian journal medical microbiology 2005 23(2)120-124.
15. Screening test for detection of Methicillin Resistance (Oxacillin Resistance) in Staphylococcus CLSI document M100-S25.Table 3E.Jan 2015.Vol.35No.3.
16. Gonzalez-Barca E, Fernandez-Sevilla A, Carratala J, Granena 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.
17. Rubio M, Palau L, Vivas JR, et al. Predominance of gram-positive microor-ganisms as a cause of septicemia in patients with hematological malignancies. Infect Control Hosp Epidemiol  1994;15:101-4.
18. Prabhash, K., Medhekar, A., Ghadyalpatil, N., Noronha, V., Biswas, S., Kurkure, P., Nair, R. and Kelkar, R. (2010), "Blood stream infections in cancer patients: A single center experience of isolates and sensitivity pattern."Indian Journal of Cancer, 47(2), 184-88.
19. Mandal, P.K, Maji, S.K., Dolai, T.K., De, R., Dutta, S., Saha, S. and Bhattacharyya, M. (2015). “Micro-organisms Associated with Febrile Neutropenia in Patients with Haematological Malignancies in a Tertiary Care Hospital in Eastern India.”Indian Journal of Hematology and Blood Transfusion,31(1), 46-50.
20. Gudiol, C., Calatayud, L., Garcia-Vidal, C., Lora-Tamayo, J., Cisnal, M., Duarte, R., Arnan, M., Marin, M., Gudiol, F. and Carratala, J. (2010). “Bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli(ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome.” Journal of Antimicrobial Chemotherapy, 65(2), 333-41.

Dr Yazhini K, MBBS., MD

Assistant Professor & Consultant Microbiolgist, Meenakshi Ammal Dental College & Meenakshi General Hospital

Address: No.12, Padmavathy nagar, 13th cross street, Thirumullaivoyal, Chennai – 600062, India