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  Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 4  |  Page : 487-490
 

An audit of febrile neutropenia cases from a rural cancer center in India


1 Department of Medical Oncology and Hematology, Malabar Cancer Center, Thallassery, Kerala, India
2 Department of Radiation Oncology, Malabar Cancer Center, Thallassery, Kerala, India
3 Department of Microbiology, and clinical laboratories, Malabar Cancer Center, Thallassery, Kerala, India

Date of Web Publication1-Feb-2016

Correspondence Address:
V M Patil
Department of Medical Oncology and Hematology, Malabar Cancer Center, Thallassery, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.175338

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 » Abstract 

Background: Data of febrile neutropenia (FN) from rural cancer centers is sparse. We did a audit of outcome of patients with FN in the period of March 2013-August 2013. The aim was to help us to develop rational antibiotic usage policies.Materials and Methods: Retrospective analysis of all consecutive patients presenting with FN. Data regarding demographic profile, tumor type, intent of treatment, chemotherapy regimen, blood culture susceptibility details, use of antibiotics, response to antibiotics and complications of FN were noted. SPSS (Statistical Product and Service Solutions) 16 was used for analysis. Results: 67 patients had FN and there were 91 episodes. The median day of presentation with FN after start of chemotherapy was 10 days. The nadir absolute neutrophil count was 161.5 and nadir platelet count 1,00,000. The median multinational association for supportive care in cancer (MASCC) Score was 24. In accordance with MASCC there were 27 high risk FN and 64 low risk FN episodes. On multivariate analysis using logistic regression MASCC score strata was the only significant variable that predicted failure to 1st line antibiotics (P = 0.03) and mortality (P = 0.01). Nine patients (9.9%) had positive isolates on blood cultures. The blood culture isolates were predominantly Gram negative (66.7%). Conclusion: The importance of developing local guidelines for rational antibiotic usage is highlighted.


Keywords: Febrile neutropenia, multinational association for supportive care in cancer score, rural cancer center


How to cite this article:
Patil V M, Chakarborty S, Kumar M S, Geetha M, Dev S, Samuel S, Ahmed G, Nayanar S K, Vineetha R, Nair C K. An audit of febrile neutropenia cases from a rural cancer center in India. Indian J Cancer 2014;51:487-90

How to cite this URL:
Patil V M, Chakarborty S, Kumar M S, Geetha M, Dev S, Samuel S, Ahmed G, Nayanar S K, Vineetha R, Nair C K. An audit of febrile neutropenia cases from a rural cancer center in India. Indian J Cancer [serial online] 2014 [cited 2019 Dec 8];51:487-90. Available from: http://www.indianjcancer.com/text.asp?2014/51/4/487/175338



 » Introduction Top


Febrile neutropenia (FN) is an emergency in medical oncology practice.[1],[2],[3],[4],[5],[6] Appropriate antibiotics and its timely use is of utmost importance in this situation. Various guidelines are been formulated by in order to expedite appropriate management in this situation.[1],[3],[7] While appropriate use of broad spectrum antibiotics are suggested in all guidelines the appropriate selection of the agents require knowledge of local antibiotic susceptibility pattern. This was highlighted by Prabhash et al. in a study from Tata Memorial Hospital (TMH) where it was seen that though cefoperazone sulbactam (CFS) is not recommended as an upfront broad spectrum antibiotic in such settings, most of the isolates were susceptible to this drug.[8],[9] Further in this study most of the isolates were Gram negative bacteria as opposed to western literature where in recent period the major isolates have been Gram positive bacteria. This predominant Gram negative pattern of isolates is also reported in other Indian studies of FN.[3],[4],[5],[8],[9],[10],[11],[12] Hence its important for each institute to regularly audit patterns of infection and antibiotic susceptibility to formulate rational antibiotic usage policies.

Our institute caters to patients hailing primarily from rural areas which are situated at some distance from the institute and available transportation facilities are limited. Guidelines for empirical antibiotic administration in the community setting are not formulated till date and as a result patients are at risk of receiving inappropriate data regarding demographic profile, tumor type, intent of treatment, chemotherapy regimen, blood culture susceptibility details, use of antibiotics, response to antibiotics and complications of FN were noted. Ate antibiotic treatment from the peripheral centers.

The present audit is the first audit of outcome of patients with FN in our center with emphasis on the isolate pattern and antibiotic sensitivity between the period of March 2013 and August 2013. The aim is to help us to develop rational antibiotic usage policies for the hospital as well as develop guidelines for initial antibiotic administration in the community basis in patients having FN after receiving chemotherapy on outpatient basis.


 » Materials and Methods Top


A retrospective audit was performed including all patients with FN treated at our institute between 1st March 2013 and 15th August 2013. At our institute all patients with documented or suspected FN were admitted, undergo mandatory blood cultures and are started on empirical broad spectrum antibiotics. The time period was chosen as our Microbiology Department started functioning with the commissioning of a BD BACTEC 9050 automatic blood culture system and Phoeni × 100 automated identification and susceptibility testing system (Becton, Dickinson and Company, New Jersey, USA).

Previous experience with patients admitted with FN had suggested that majority of the isolates were sensitive to either CFS and amikacin (AMI) or piperacillin-tazobactam (PIP-TAZ). The choice of use of these antibiotics was division specific, with the hemato-oncology division using PIP-TAZ and the solid tumor division using CFS with AMI as the 1st line empirical therapy. Antibiotics were continued till defervescence of fever and till recovery of the neutrophil count. Gram positive and fungal coverage were provided as per standard guidelines.[1],[7] In case of no defervescence of fever for more than 48 h or deterioration in clinical status 2nd line antibiotics (Carbapenems) were used.

In the present audit the requirement of 2nd line antibiotics, inotropic support while on 1st line antibiotics, ventilatory support on 1st line antibiotics or mortality were considered as failure of the 1st line antibiotics. Data regarding demographic profile, tumor type, intent of treatment, chemotherapy regimen, blood culture susceptibility details, use of antibiotics, response to antibiotics and complications of FN were noted. The multinational association for supportive care in cancer (MASCC) Risk Index was calculated retrospectively for each episode.[13] Each episode was taken as a separate event.

Statistical analysis was done with SPSS (Statistical Product and Service Solutions) version 16. Descriptive statistics have been reported for demographic data as well as for antibiotic sensitivity data. Multivariate analysis was done using logistic regression for finding factors associated with antibiotic failure and mortality. The variable included were MASCC score, presence of comorbidities, day of FN, type of tumor and intention of treatment. These variables were included as categorical variables and the enter method was used for the regression model and P < 0.05 were taken as significant. The MASCC score sensitivity, specificity and positive predictive value (PPV) was calculated for mortality related to FN.


 » Results Top


67 patients were evaluable subject to the inclusion criteria. 17 patients had more than a single episode of FN. The basic demographic details and baseline information of these 67 patients is shown in [Table 1]. The three commonest cancer sites in these patients were breast (n = 24; 35.8%), acute myeloid leukemia (n = 9; 13.4%) and lung (n = 6; 9.0%). The three commonest regimen associated with FN were FEC (n = 18, 26.9%), docetaxel (n = 6, 9.0%) and paclitaxel carboplatin (n = 4, 6.0%). 47 (70.0%) patients had no comorbidities while 4 (6.0%) patients had more than single comorbidity. Four patients (6.0%) had FN during concurrent chemoradiation.
Table 1: Baseline profile of patients

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Total 91 episodes of FN were identified in these 67 patients. Subsequent analysis is reported taking each episode as a discrete event. The median day of presentation with FN after start of chemotherapy was 10 days. The nadir absolute neutrophil count (ANC) was 161.5 and nadir platelet count 1,00,000. The median MASCC Score was 24. In accordance with MASCC there were 27 high risk FN and 64 low risk FN episodes. The details of antibiotic use are shown in [Table 2]. There were significant differences in the MASCC scores, mean age, nadir platelet counts and ANC counts between patients with solid and hematological malignancies as shown in [Table 3].
Table 2: Treatment details of febrile neutropenia

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Table 3: Differences between solid and hematological malignancies

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On multivariate analysis using logistic regression MASCC score strata was the only significant variable that predicted failure to 1st line antibiotics (P = 0.03) and mortality (P = 0.01). The sensitivity, specificity, negative predictive value (NPV) and PPV of MASCC score in predicting mortality were 85.7% (95% confidence interval [CI] 42.0-99.2%), 75% (95 CI 64.0-83.5%), 98.4% (90.4-99.9%) and 22.2% (9.3-42.7%) respectively.

Nine patients (9.9%) had positive isolates on blood cultures. The blood culture isolates were predominantly Gram negative (66.7%). The details of isolates are shown in [Table 4]. The susceptibility pattern of these isolates has been depicted in a series of bar diagram in [Figure 1].
Table 4: Details about bacterial isolates

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Figure 1: Praportional bar diagram showing sensitivity pattern of bacterial isolates

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 » Discussion Top


Initial management of FN is dictated by local antibiotic sensitivity pattern which determines the initial empirical antibiotic policy. This data is of utmost importance as the local bacterial sensitivity pattern differs across countries, institutes and over the period of time. [Table 5] shows reported antibiotic profile and sensitivity pattern across India in major institutes.[9],[10],[12] This pattern of isolate differs from that reported in west, where Gram positive bacterial isolates are predominant.
Table 5: Details about bacterial isolatessensitivity pattern

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The local antibiotic pattern in major centers of India shows that substantial amount of Gram negative bacterial isolates in India are sensitive to CFS.[8],[9],[11],[10],[12] This antibiotic is not mentioned in major guidelines but in a recent trial from Demir et al. comparison of CFS against monotherapy with carbapenem did show that both antibiotics are equally effective and had a success rate of 99%.[14] A success rate of 83.3% was seen in our solid cancer patients receiving CFS with aminoglycoside while a success rate of 58.6% was seen in our hematological patients receiving PIP-TAZ. Though numerically CFS combination looks better that PIP-TAZ this is a non-random comparison these both groups were not comparable. As [Table 3] shows patients with hematological malignancies had more severe hematological toxicity as well as worse MASCC scores as compared to those with solid malignancies. As seen in [Table 3] there was no statistically significant difference in the response rate to 1st line antibiotics in patients with solid or hematological malignancies.

Use of monotherapy with an antipseudomonal 3rd and 4th generation cephalosporins or carbapenems or PIP-TAZ is recommended by western guidelines.[1],[7] However, this recommendation is based on a meta-analysis done by Furno et al. which revealed that addition aminoglycoside doesn't add to the efficacy.[15] However, this analysis is mainly based on western literature where profile and sensitivity pattern of bacterial isolates is different from those seen in India. Consistently major Indian centers have shown presence of resistant Gram negative isolates in there samples.[9],[10],[12]

We selected period from March to august 2013. Prior to March, cultures were done from outside laboratories where conventional culture was performed. The results of these episodes were not included as the BACTEC system has demonstrated to improve the detection of significant isolates from normally sterile body fluids as compared to conventional cultures especially for fastidious organisms.[16] We wanted this data to be our baseline against which future comparisons of both are clinical data and bacterial isolates would be done.

In rural centers like ours majority of the patients live more than 1 h away from the treatment centers with poor access to well-equipped peripheral hospitals and ambulances for transportation. Hence we admit all patients presenting with FN although Western guidelines recommend treatment of low risk patients on out-patient basis. Quinolones have been used as the 1st line antibiotics in low risk patients in the solid tumor division. However, such practice is associated with high failure rates as was seen in our analysis where only 29% of patient responded to 1st line quinolone antibiotics. This finding runs counter to our previous experience where majority of the isolates were sensitive to quinolones. In addition this finding highlights the importance of regular audits for ensuring empirical antibiotic policies remain effective.

MASCC index is a validated tool use for categorization of FN into different risk.[15] In our data it was seen that response to 1st line antibiotics were significantly lower in high risk FN (40.7%) as opposed to in low risk FN (67%). The predictive value of MASCC has been debated for long in India.[17] In the present study also MASCC index had 98% NPV in predicting mortality. Even in multivariate analysis MASCC strata was the only significant factor predicting failure of 1st line antibiotic and mortality. However, given the poor efficacy of quinolones as 1st line antibiotics in our it is uncertain how the MASCC index can be used for outpatient treatment of low risk FN patients. The MASCC index may however, help us to implement a rapid change to carbapenems within the first 24 h especially in admitted patients who do not respond to initial antibiotics.

Our data shows the importance of adequate selection of antibiotics as the lack of response to 1st line antibiotics was significantly associated with risk of mortality. Our success rates might seem to be lower than those reported from major centers in India. This may be related to the rural location of our center as well as the nature of patients we cater to. Majority of our patients presented to us at a median of 10 days post-chemotherapy. This is different from that reported by other centers in India where majority of patients reported by day 8.[18] This may reflect a lack of awareness regarding the importance of the warning signs of infection.

With this respect to we have made a recommendation in our local hospital policy which are shown in [Table 6]. We intend to review our data after a year to see the success or failure for these implementations.
Table 6: Recommendations made to local infection control committee

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 » Conclusion Top


FN is a medical complication whose treatment guidelines should be locally derived and implemented.

 
 » References Top

1.
Cameron D. Management of chemotherapy-associated febrile neutropenia. Br J Cancer 2009;101 Suppl 1:S18-22.  Back to cited text no. 1
    
2.
Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American society of clinical oncology clinical practice guideline. J Clin Oncol 2013;31:794-810.  Back to cited text no. 2
    
3.
Klastersky J, Awada A, Paesmans M, Aoun M. Febrile neutropenia: A critical review of the initial management. Crit Rev Oncol Hematol 2011;78:185-94.  Back to cited text no. 3
    
4.
Slavin MA, Thursky KA. Outpatient therapy for fever and neutropenia is safe but implementation is the key. J Clin Oncol 2013;31:1128-9.  Back to cited text no. 4
    
5.
Bothra M, Seth R, Kapil A, Dwivedi SN, Bhatnagar S, Xess I. Evaluation of predictors of adverse outcome in febrile neutropenic episodes in pediatric oncology patients. Indian J Pediatr 2013;80:297-302.  Back to cited text no. 5
    
6.
Oberoi S, Suthar R, Bansal D, Marwaha RK. Febrile neutropenia: Outline of management. Indian J Pediatr 2013;80:138-43.  Back to cited text no. 6
    
7.
de Naurois J, Novitzky-Basso I, Gill MJ, Marti FM, Cullen MH, Roila F, et al. Management of febrile neutropenia: ESMO clinical practice guidelines. Ann Oncol 2010;21 Suppl 5:v252-6.  Back to cited text no. 7
    
8.
Prabhash K, Medhekar A, Biswas S, Kurkure P, Nair R, Kelkar R. Comparison of in vitro activities of ceftazidime, piperacillin-tazobactam, and cefoperazone-sulbactam, and the implication on empirical therapy in patients with cancer. Indian J Cancer 2009;46:318-22.  Back to cited text no. 8
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9.
Prabhash K, Medhekar A, Ghadyalpatil N, Noronha V, Biswas S, Kurkure P, et al. Blood stream infections in cancer patients: A single center experience of isolates and sensitivity pattern. Indian J Cancer 2010;47:184-8.  Back to cited text no. 9
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10.
Ghosh I, Raina V, Kumar L, Sharma A, Bakhshi S, Thulkar S, et al. Profile of infections and outcome in high-risk febrile neutropenia: Experience from a tertiary care cancer center in India. Med Oncol 2012;29:1354-60.  Back to cited text no. 10
    
11.
Roy V, Saxena D, Agarwal M, Bahadur AK, Mishra B. Use of antimicrobial agents and granulocyte colony stimulating factors for febrile neutropenia in cancer patients in a tertiary care hospital in India. Indian J Cancer 2010;47:430-6.  Back to cited text no. 11
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12.
Karanwal A, Parikh B, Goswami P, Panchal H, Parekh B, Patel K. Review of clinical profile and bacterial spectrum and sensitivity patterns of pathogens in febrile neutropenic patients in hematological malignancies: A retrospective analysis from a single center. Indian J Med Paediatr Oncol 2013;34:85.  Back to cited text no. 12
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13.
Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, et al. The multinational association for supportive care in cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 2000;18:3038-51.  Back to cited text no. 13
    
14.
Demir HA, Kutluk T, Ceyhan M, Yağcı-Küpeli B, Akyüz C, Cengiz B, et al. Comparison of sulbactam-cefoperazone with carbapenems as empirical monotherapy for febrile neutropenic children with lymphoma and solid tumors. Pediatr Hematol Oncol 2011;28:299-310.  Back to cited text no. 14
    
15.
Furno P, Bucaneve G, Del Favero A. Monotherapy or aminoglycoside-containing combinations for empirical antibiotic treatment of febrile neutropenic patients: A meta-analysis. Lancet Infect Dis 2002;2:231-42.  Back to cited text no. 15
    
16.
Cetin ES, Kaya S, Demirci M, Aridogan BC. Comparison of the BACTEC blood culture system versus conventional methods for culture of normally sterile body fluids. Adv Ther 2007;24:1271-7.  Back to cited text no. 16
    
17.
Bajpai J, Prabhash K, Medhekar A, Nair R, Kurkure P, Ghadyalpatil N, et al. Performance of MASCC score and other factors for identifying low-risk febrile-neutropenic cancer patients. J Clin Oncol Meet Abstr 2010; Vol 28, No 15_suppl (May 20 Supplement), 2010: e19533:e19533.  Back to cited text no. 17
    
18.
Bhosale B, Patil V, Muddu V, Randeep S, Dwivedi P, Noronha V, et al. Predicting complications of chemotherapy-induced febrile neutropenia: A single-center experience;31:e20678.  Back to cited text no. 18
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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