Abstract

INTRODUCTION

Febrile neutropenia (FN) is a common complication of cancer treatment. With the development of more aggressive chemotherapy regimens for hematological malignancies, the survival of these patients has improved. At the same time, these patients frequently succumb to febrile neutropenia, which is the major cause of morbidity and mortality. Studies have reported that 48-60% of patients admitted with febrile neutropenia have an infection, which can be life-threatening as well.[1]

Over the past decade, there has been a considerable change in the spectrum and antibiotic susceptibility patterns of pathogens causing infection in FN patients. Knowledge of locally prevalent pathogens and their sensitivities is essential as it helps to guide antimicrobial therapy in neutropenic patients.[2] The most effective empirical antimicrobial regimen must be rapidly administered to FN patients as delay in the initiation of treatment may result in septicemic shock and thus increase mortality.

To have an insight into the clinical profile of these FN patients as well as spectrum of antimicrobial susceptibility pattern, we have done this retrospective study.

MATERIALS AND METHODS

All clinical and microbiological data were collected retrospectively from FN patients admitted at our institute between June 2011 and December 2011. The inclusion criteria's include hematological malignancy patients having FN and culture positive report. Patient population consisted of both adults and pediatrics with acute and chronic leukemia, myelodysplastic syndrome (MDS), multiple myeloma and other malignancies. FN was defined as fever greater than 38.5°C on one occasion and with an absolute neutrophil count (ANC) of less than 0.5 × 109/L. Cultures were taken from blood in all cases and from urine, stool, tracheal aspirate, sputum or wound depending upon identifiable focus of infection. Blood cultures were processed using the Bactec blood culture system. Organisms were identified according to routine bacteriological procedures. Antibiotic susceptibility testing was performed by disc diffusion method. Results of these were interpreted according to the Clinical Laboratory Standards Institutes guidelines.

RESULTS

A total of 23 (12 males and 11 females) patients with chemotherapy induced FN were analyzed. Table 1 shows the characteristics of these patients. The mean age of the study population was 35 years (range 16-63 years). Majority of patients were of acute leukemia (78%), acute myeloid leukemia (AML) 48% (11/23), acute lymphoblastic leukemia (ALL) 30% (7/23), one patient each of chronic myeloid leukemia (CML), MDS, multiple myeloma, and two patients of other diagnosis. Majority of patients had developed FN during the induction phase of acute leukemia treatment. Most common presenting symptoms were fever, cough, dyspnea and diarrhea.

Table 1

DISCUSSION

Over the past 25 years, there has been a shift in the microbiological spectrum from gram negative to gram positive organisms at many cancer centers.[3] The possible reasons for this shift are better control of gram negative infections with newer ultra-broad spectrum antibiotics, fluoroquinolone prophylaxis, and increase use of long dwelling intravenous devices.[4,5] This study demonstrates that gram negative organisms are still the predominant pathogens causing bacteremia in FN patients. The spectrum of bacterial isolates in our study is similar to what has been reported in both local and international studies. Coagulase negative staphylococci were the most commonly isolated gram positive organisms.[3,6] E. coli was the most frequently isolated gram negative pathogen.[3,7]

This study shows that C/Su and amikacin may represent current best empirical antibiotics for suspected gram negative infections while for gram positive infections; vancomycin and linezolid may play the same role. As soon as the culture sensitivity report comes, antibiotics should be modified for best outcomes. Currently, P/T, amikacin, I/C and C/Su are the most common empirical antibiotics used at our institute.

Our study shows that FN is one of the major causes of morbidity and mortality in patients of hematological malignancies. These patients may not present with any obvious source of infection except blood stream infection. Hence, in all patients suspected of FN, blood culture sensitivity should be sent if possible before the first dose of antibiotics. Furthermore, these patients generally have associated anemia and thrombocytopenia, which should be adequately supported with blood transfusion. Growth factors should be used except in situations like during induction regimens of acute leukemia.

CONCLUSIONS

Induction phase of treatment of acute leukemia are the major cause of FN in hematological malignancies at our institute and gram negative organisms are the predominant organisms with E. coli as major isolate while S. aureus represents the most common gram positive organism. Amikacin and C/Su appears to be initial antibiotic appropriate to cover most gram negative pathogens while vancomycin to be added for suspected gram positive infections. FN represents a major cause of morbidity and mortality in hematological malignancy patients, high index of suspicion and early empirical antibiotics with supportive care are main interventions to reduce high mortality for these patients. Antibiotics should be modified according to culture sensitive report as soon as possible. Continuous surveillance of the spectrum of locally prevalent pathogens and their susceptibility patterns is essential for formulation of therapeutic regimens for chemotherapy induced FN patients.

ACKNOWLEDGMENTS

Footnotes