About Author:
Uday Venkat Mateti1*, Srikala Patha2
1. Department of Pharmacy Practice & Pharm.D, St Peter’s Institute of Pharmaceutical Sciences, Rohini Hospital, Kakatiya University, Warangal, India
2. Department of Pharmacy Practice, Bharat Institute of Technology (Pharmacy), KIMS Hospital, JNTU, Hyderabad, India.
Abstract:
The mortality rate of febrile neutropenia (FN) has diminished steadily but remains significant. Overall mortality rates are 5% in patients with solid tumors (1% in low-risk patients) and as high as 11% in some hematological malignancies. Piperacillin/Tazobactam is a β-lactam/β-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive, Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/Tazobactam is effective and well tolerated in patients with febrile neutropenia. Guidelines for the Management of Febrile Neutropenia in Oncology Patients and the 2010 National Comprehensive Cancer Network (NCCN) Prevention and treatment for febrile neutropenia recommends as initial treatment in patients with FN who are at high risk of serious infections. In comparative clinical trials against various other antibacterial regimens. Piperacillin/Tazobactam has shown higher clinical success rates, particularly in the treatment of patients with febrile neutropenia. Piperacillin/Tazobactam has shown clinical as well as the economic advantages over other antibacterial regimens in the treatment of febrile episodes in patients with neutropenia. It is likely to reduce overall treatment costs of moderate to severe febrile neutropenia by increasing initial treatment success thereby reducing the length of hospital stay and the use of additional antibacterials. Present data regarding clinical efficacy, safety and costs would support the use of Piperacillin/Tazobactam as an empirical first-line option in moderate to severe febrile episodes in patients with neutropenia.
The mortality rate of febrile neutropenia (FN) has diminished steadily but remains significant. Overall mortality rates are 5% in patients with solid tumors (1% in low-risk patients) and as high as 11% in some hematological malignancies. Piperacillin/Tazobactam is a β-lactam/β-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive, Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/Tazobactam is effective and well tolerated in patients with febrile neutropenia. Guidelines for the Management of Febrile Neutropenia in Oncology Patients and the 2010 National Comprehensive Cancer Network (NCCN) Prevention and treatment for febrile neutropenia recommends as initial treatment in patients with FN who are at high risk of serious infections. In comparative clinical trials against various other antibacterial regimens. Piperacillin/Tazobactam has shown higher clinical success rates, particularly in the treatment of patients with febrile neutropenia. Piperacillin/Tazobactam has shown clinical as well as the economic advantages over other antibacterial regimens in the treatment of febrile episodes in patients with neutropenia. It is likely to reduce overall treatment costs of moderate to severe febrile neutropenia by increasing initial treatment success thereby reducing the length of hospital stay and the use of additional antibacterials. Present data regarding clinical efficacy, safety and costs would support the use of Piperacillin/Tazobactam as an empirical first-line option in moderate to severe febrile episodes in patients with neutropenia.
Introduction:
Though there have been major advances in prevention and treatment of febrile neutropenia (FN) febrile neutropenia still remains one of the most feared complications of cancer chemotherapy. It is a major cause of morbidity, healthcare resource use, and results in delays and dose reductions in chemotherapy which compromise efficacy. The mortality rate of febrile neutropenia (FN) has diminished steadily but remains significant. Overall mortality rates are 5% in patients with solid tumors (1% in low-risk patients) and as high as 11% in some hematological malignancies.1 As such, febrile neutropenia (FN) requires prompt treatment with Piperacillin -Tazobactam since it may be associated with life-threatening infections. Piperacillin/Tazobactam is a β-lactam/β-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive, Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin / Tazobactam is effective and well tolerated in patients with febrile neutropenia. Guidelines for the Management of Febrile Neutropenia in Oncology Patients and the 2010 National Comprehensive Cancer Network (NCCN) Prevention and treatment for febrile neutropenia recommends as initial treatment in patients with FN who are at high risk of serious infections. In comparative clinical trials against various other antibacterial regimens, Piperacillin/Tazobactam has shown higher clinical success rates, particularly in the treatment of patients with febrile neutropenia. The studies which are supported to the Piperacillin/Tazobactam in the management of Febrile Neutropenia are explained in the table 1.2,3,4,5
Though there have been major advances in prevention and treatment of febrile neutropenia (FN) febrile neutropenia still remains one of the most feared complications of cancer chemotherapy. It is a major cause of morbidity, healthcare resource use, and results in delays and dose reductions in chemotherapy which compromise efficacy. The mortality rate of febrile neutropenia (FN) has diminished steadily but remains significant. Overall mortality rates are 5% in patients with solid tumors (1% in low-risk patients) and as high as 11% in some hematological malignancies.1 As such, febrile neutropenia (FN) requires prompt treatment with Piperacillin -Tazobactam since it may be associated with life-threatening infections. Piperacillin/Tazobactam is a β-lactam/β-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive, Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin / Tazobactam is effective and well tolerated in patients with febrile neutropenia. Guidelines for the Management of Febrile Neutropenia in Oncology Patients and the 2010 National Comprehensive Cancer Network (NCCN) Prevention and treatment for febrile neutropenia recommends as initial treatment in patients with FN who are at high risk of serious infections. In comparative clinical trials against various other antibacterial regimens, Piperacillin/Tazobactam has shown higher clinical success rates, particularly in the treatment of patients with febrile neutropenia. The studies which are supported to the Piperacillin/Tazobactam in the management of Febrile Neutropenia are explained in the table 1.2,3,4,5
Table 1: The studies which are supported to the Piperacillin / Tazobactam in the management of Febrile Neutropenia
Authors/ Guidelines
|
Study Title
|
Outcomes of the studies
|
| NCCN guidelines 2010 for febrile neutropenia | Empirical antibiotic therapy for febrile neutropenia | According to this Guidelines Piperacillin/Tazobactam is the initial Empirical therapy in the Management of Febrile Neutropenia |
| Takashi Saito et. al, 2011 | Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies | In the present study, the overall efficacy rate was 57.0% in the Fourth-Generation Cephalosporins group and 59.2% in the Piperacillin/Tazobactam group. No adverse drug reaction requiring discontinuation or switching of the study treatments was noted in any of the patients. |
| Guidelines for the Management of Febrile Neutropenia in Oncology Patients, 2011 | Summary of Guidelines for the Immediate Management of Suspected or Confirmed Febrile Neutropenia in Oncology Patients |
According
to this Guidelines Piperacillin/Tazobactam is the initial treatment in
the Management of Febrile Neutropenia with the dose of 4.5gIV TDS for 14
days. Piperacillin/Tazobactam dose should be reduced in renal impairment |
| E. J. Bow et. al., 2006 | A Randomized, Open-Label, Multicenter Comparative Study of the Efficacy and Safety of Piperacillin-Tazobactam and Cefepime for the Empirical Treatment of Febrile Neutropenic Episodes in Patients with Hematologic Malignancies | Out of 528 subjects (265 received Piperacillin-Tazobactam and 263 received Cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for Piperacillin-Tazobactam at all time points (P ?.0001). This trial, taken together with other large clinical trials, firmly establishes the safety and efficacy of Piperacillin-Tazobactam monotherapy for the empirical treatment of the febrile neutropenic patients with cancer |
| Young et. al., 2002 |
Piperacillin/Tazobactam in Moderate to Severe Bacterial Infections | Piperacillin/Tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment febrile episodes in patients with neutropenia. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of Piperacillin/Tazobactam as an empirical first-line option in moderate to severe bacterial infections. |
Advantages of Piperacillin-Tazobactam:
Cephalosporins resistant Gram-negative bacteremia in febrile neutropenic patients with hematological malignancies has increased significantly, particularly in the ICU, in the past decade. The main mechanism accountable for is the emergence of extended-spectrum beta-lactamases (ESBLs). These plasmid-mediated beta-lactamases confer resistance to majority of the broad-spectrum beta-lactam antibiotics like third- and fourth-generation cephalosporins. Piperacillin/Tazobactam is currently considered as the drug of choice for these pathogens. Prevention and control measures are important because of the multiresistant nature of these pathogens. Such traditional infection control measures as contact precautions are recommended. This type of antimicrobial resistance appears to be particularly influenced by antibiotic use. Antibiotic control measures may also be a very important intervention in controlling the spread of ESBLs.6
Cephalosporins resistant Gram-negative bacteremia in febrile neutropenic patients with hematological malignancies has increased significantly, particularly in the ICU, in the past decade. The main mechanism accountable for is the emergence of extended-spectrum beta-lactamases (ESBLs). These plasmid-mediated beta-lactamases confer resistance to majority of the broad-spectrum beta-lactam antibiotics like third- and fourth-generation cephalosporins. Piperacillin/Tazobactam is currently considered as the drug of choice for these pathogens. Prevention and control measures are important because of the multiresistant nature of these pathogens. Such traditional infection control measures as contact precautions are recommended. This type of antimicrobial resistance appears to be particularly influenced by antibiotic use. Antibiotic control measures may also be a very important intervention in controlling the spread of ESBLs.6
Cost analysis of
Piperacillin/Tazobactam has been variable, in part, because of
differences in specific costs included. The US cost analysis shows that
Piperacillin/Tazobactam has lower total medical costs than other antibiotics. Intravenous antibiotics: acquisition costs per febrile neutropenia episode are summarized in the table 2.7
Table 2: Intravenous antibiotics: acquisition costs per febrile neutropenia episode:
Drug name
|
Dosage/day(mg)
|
Cost per vial/unit
|
Cost/day
|
Total cost/day
|
Days/episode
|
Total cost/episode
|
IV ceftazidime
|
2g q8hr; 6g/d
|
$17.90 for 2g
|
$53.7
|
$53.7
|
8.5
|
$456.45
|
IV Imipenem- Cilastatin
|
1-2g/d ; 2g/d
|
$12 for 0.5g
|
$48.00
|
$48.00
|
8.5
|
$408.00
|
IV Piperacillin-Tazobactam
|
4.5g q8hr; 13.5g/d
|
$15.79 for 4.5g
|
$47.37
|
$47.37
|
8.5
|
$402.64**
|
IV Amikacin +
Piperacillin-Tazobactam
|
15-22.5mg/kg daily = 1406mg/d
4.5g every 6h = 18g/d
|
$10.14 for 500mg
$15.79 for 4.5g
|
$28.52
$63.16
|
$91.68
|
8.5
|
$779.28
|
IV Amikacin +
Ceftazidime
|
15-22.5mg/kg daily = 1.406g/d
3-6g/d; assume 4.5g/d
|
$10.14 for 0.5g
$17.90 for 2g
|
$28.52
v40.28
|
$68.79
|
8.5
|
$584.72
|
Conclusion:
Piperacillin/Tazobactam has shown clinical as well as the economic advantages over other antibacterial regimens in the treatment of febrile episodes in patients with neutropenia. It is likely to reduce overall treatment costs of moderate to severe febrile neutropenia by increasing initial treatment success thereby reducing the length of hospital stay and the use of additional antibacterials. Present data regarding clinical efficacy, safety and costs would support the use of Piperacillin/Tazobactam as an empirical first-line option in moderate to severe febrile episodes in patients with neutropenia.
Piperacillin/Tazobactam has shown clinical as well as the economic advantages over other antibacterial regimens in the treatment of febrile episodes in patients with neutropenia. It is likely to reduce overall treatment costs of moderate to severe febrile neutropenia by increasing initial treatment success thereby reducing the length of hospital stay and the use of additional antibacterials. Present data regarding clinical efficacy, safety and costs would support the use of Piperacillin/Tazobactam as an empirical first-line option in moderate to severe febrile episodes in patients with neutropenia.
References:
1. Marti F, Cullen MH, Roila F. Management of febrile neutropenia: ESMO Clinical Recommendations. Annals of Oncology 2009; 20(4) : p. iv166-iv169.
2. Takashi S, Tatsuo I, Junya K, Miki N, Shunji T, Yutaka I, et.al,. Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies. International Journal of Clinical Medicine 2011; 2 (1): p. 18-22.
3. Michael G, Maria T. NCCN guidelines for febrile neutropenia. Clinical oncology news: 2010. P. 115-122.
4. Guidelines for the Management of Febrile Neutropenia in Oncology Patients, 2011. URL: nuhnet/diagnostics_clinical_support/antibiotics [Last updated on 21 June 2011].
5. Bow EJ, Rotstein C, Noskin GA, Laverdiere M, Schwarer AP, Segal BH, Seymour JF, Szer J, Sanche S. A Randomized, Open-Label, Multicenter Comparative Study of the Efficacy and Safety of Piperacillin-Tazobactam and Cefepime for the Empirical Treatment of Febrile Neutropenic Episodes in Patients with Hematologic Malignancies. Clin Infect Dis. 2006 Aug 15;43(4):447-59.
6. Chong Y, Yakushiji H, Ito Y, Kamimura T. Cefepime-resistant Gram-negative bacteremia in febrile neutropenic patients with hematological malignancies. Int J Infect Dis. 2010 Sep;14 Suppl 3:e171-5.
7. Dominguez AG, Pérez M, SantosL, Sanz A, Rubio C. Cost-Effectiveness of Piperacillin-Tazobactam Versus Ceftazidime in Patients with Febrile Neutropenia. Value in Health 1998; 1(1): P.68.
1. Marti F, Cullen MH, Roila F. Management of febrile neutropenia: ESMO Clinical Recommendations. Annals of Oncology 2009; 20(4) : p. iv166-iv169.
2. Takashi S, Tatsuo I, Junya K, Miki N, Shunji T, Yutaka I, et.al,. Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies. International Journal of Clinical Medicine 2011; 2 (1): p. 18-22.
3. Michael G, Maria T. NCCN guidelines for febrile neutropenia. Clinical oncology news: 2010. P. 115-122.
4. Guidelines for the Management of Febrile Neutropenia in Oncology Patients, 2011. URL: nuhnet/diagnostics_clinical_support/antibiotics [Last updated on 21 June 2011].
5. Bow EJ, Rotstein C, Noskin GA, Laverdiere M, Schwarer AP, Segal BH, Seymour JF, Szer J, Sanche S. A Randomized, Open-Label, Multicenter Comparative Study of the Efficacy and Safety of Piperacillin-Tazobactam and Cefepime for the Empirical Treatment of Febrile Neutropenic Episodes in Patients with Hematologic Malignancies. Clin Infect Dis. 2006 Aug 15;43(4):447-59.
6. Chong Y, Yakushiji H, Ito Y, Kamimura T. Cefepime-resistant Gram-negative bacteremia in febrile neutropenic patients with hematological malignancies. Int J Infect Dis. 2010 Sep;14 Suppl 3:e171-5.
7. Dominguez AG, Pérez M, SantosL, Sanz A, Rubio C. Cost-Effectiveness of Piperacillin-Tazobactam Versus Ceftazidime in Patients with Febrile Neutropenia. Value in Health 1998; 1(1): P.68.
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