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CC BY-NC-ND 4.0 · South Asian J Cancer 2022; 11(04): 370-377
DOI: 10.1055/s-0042-1745834
Original Article
Neuro-Oncology

Once-a-Day Ceftriaxone–Amikacin Combination as Empiric Antibiotic Therapy to Enable Outpatient Management of Febrile Neutropenia in Children—16-Year Experience from a Single Institute

Shailesh Kanvinde
1   Department of Pediatric Hematology and Oncology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
,
Atul Mulay
2   Department of Nephrology and Clinical Epidemiology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
,
Anand Deshpande
3   Department of Pediatrics, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
,
Chetan Deshmukh
4   Department of Medical Oncology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
,
Sampada Patwardhan
5   Department of Microbiology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
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Abstract

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Shailesh Kanvinde

Background To enable outpatient department (OPD) management of febrile neutropenia (FN), we used once-a-day (OD) ceftriaxone–amikacin (CFT-AMK) as empiric antibiotic therapy. Our experience over 16-year period is presented.

Methods This was a retrospective study conducted from January2002 to December2017. Inclusion criteria were <18 years of age, undergoing cancer chemotherapy, and having FN. Exclusion criteria were FN after palliative chemotherapy, bone marrow transplantation, or at diagnosis of malignancy. Empiric CFT-AMK was used in all, except those having respiratory distress, hypotension, altered sensorium, paralytic ileus, or clinical evidence of peritonitis. Admission criteria were age <1 year, acute myeloid leukemia (AML) chemotherapy, poor performance status, need for blood transfusions, convenience, insurance, or persistent fever >48 to 72 hours after CFT-AMK. Outcomes analyzed were response (defervescence within 48–72 hours), OPD management, antibiotic upgrade, and mortality. AML diagnosis, >7 days to absolute neutrophil count >0.5 × 109/L, poor performance status, and malignancy not in remission were considered high-risk FN criteria.

Results CFT-AMK was given in 877/952 (92.2%) FN episodes. Seventy-six percent had hematolymphoid malignancies. Response, antibiotic upgrade, and mortality were seen in 85.7 and 65.5% (p < 0.0001), 15 and 45.5% (p < 0.0001), and 0 and 2% (p = 0.003) of low- and high-risk patients, respectively. Treatment was started in OPD in 52%, of which 21.6% required subsequent admission. Of those initially admitted, early discharge (hospital stay < 5 days) was possible in 24.6%. Forty-one percent episodes were managed entirely on OPD. Overall, 80% of low-risk and 42% of high-risk episodes received treatment wholly or partially on OPD.

Conclusion Our results show empiric OD CFT-AMK allows OPD management for most of the low-risk and a proportion of high-risk FN following chemotherapy in children, without compromising clinical outcomes.

Keywords

febrile neutropenia - outpatient management - ceftriaxone–amikacin

Authors' Contribution

S.K. designed the study; helped in data collection and analysis, and manuscript preparation. A.M. designed the study; helped in data analysis and critical review of manuscript. A.D. and S.P. helped in data collection and critical review of manuscript. C.D. helped in data analysis and manuscript preparation and review.


Ethics

Institutional ethics committee approval: DMHRC Code—IHR_2021_Jan_SK_391; Dated: February 3, 2021. The study was approved by the institutional ethics committee.


Financial Support

None.




Publication History

Article published online:
02 September 2022

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  • References

  • 1 Charnas R, Lüthi AR, Ruch W. Writing Committee for the International Collaboration on Antimicrobial Treatment of Febrile Neutropenia in Children. Once daily ceftriaxone plus amikacin vs. three times daily ceftazidime plus amikacin for treatment of febrile neutropenic children with cancer. Pediatr Infect Dis J 1997; 16 (04) 346-353
    CrossrefPubMedGoogle Scholar
  • 2 The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. Ann Intern Med 1993; 119 (7 Pt 1): 584-593
    CrossrefPubMedGoogle Scholar
  • 3 Smith L, Will AM, Williams RF, Stevens RF. Ceftriaxone vs. azlocillin and netilmicin in the treatment of febrile neutropenic children. J Infect 1990; 20 (03) 201-206
    CrossrefPubMedGoogle Scholar
  • 4 Cornely OA, Bethe U, Salzberger B. et al. Randomized controlled monocentric comparison of once daily ceftriaxone with tobramycin and cefotaxime three times daily with tobramycin in neutropenic fever. Ann Hematol 2001; 80 (02) 103-108
    CrossrefPubMedGoogle Scholar
  • 5 Leoni F, Ciolli S, Pascarella A, Fanci R, Caporale R, Rossi Ferrini P. Ceftriaxone plus conventional or single-daily dose amikacin versus ceftazidime/amikacin as empiric therapy in febrile neutropenic patients. Chemotherapy 1993; 39 (02) 147-152
    CrossrefPubMedGoogle Scholar
  • 6 Karthaus M, Cornely OA. Ceftriaxone in febrile neutropenia. J Chemother 2003; 15 (03) 211-219
    CrossrefPubMedGoogle Scholar
  • 7 Karthaus M, Wolf HH, Kämpfe D. et al. Ceftriaxone monotherapy in the treatment of low-risk febrile neutropenia. Chemotherapy 1998; 44 (05) 343-354
    CrossrefPubMedGoogle Scholar
  • 8 Pession A, Prete A, Paolucci G. Cost-effectiveness of ceftriaxone and amikacin as single daily dose for the empirical management of febrile granulocytopenic children with cancer. Chemotherapy 1997; 43 (05) 358-366
    CrossrefPubMedGoogle Scholar
  • 9 Sahu S, Bapna A, Pai SK, Nair CN, Kurkure PA, Advani SH. Outpatient antimicrobial protocol for febrile neutropenia: a nonrandomized prospective trial using ceftriaxone, amikacin, and oral adjuvant agents. Pediatr Hematol Oncol 1997; 14 (03) 205-211
    CrossrefPubMedGoogle Scholar
  • 10 Ponraj M, Dubashi B, Harish BH. et al. Cefepime vs. cefoperazone/sulbactam in combination with amikacin as empirical antibiotic therapy in febrile neutropenia. Support Care Cancer 2018; 26 (11) 3899-3908
    CrossrefPubMedGoogle Scholar
  • 11 Uppuluri R, Ramachandrakurup S, Vaidhyanathan L, Kandath S, Subburaj D, Raj R. Changing trends in the use of granulocyte transfusions in neutropenic children with sepsis in India. Indian J Hematol Blood Transfus 2017; 33 (02) 207-210
    CrossrefPubMedGoogle Scholar
  • 12 Meena JP, Gupta AK, Seth R. Outcomes of febrile neutropenia in children with cancer managed on an outpatient basis: a report from tertiary care hospital from a resource-limited setting. J Pediatr Hematol Oncol 2020; 42 (08) 467-473
    CrossrefPubMedGoogle Scholar
  • 13 Lehrnbecher T, Robinson P, Fisher B. et al. Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update. J Clin Oncol 2017; 35 (18) 2082-2094
    CrossrefPubMedGoogle Scholar
  • 14 Scheler M, Lehrnbecher T, Groll AH. et al. Management of children with fever and neutropenia: results of a survey in 51 pediatric cancer centers in Germany, Austria, and Switzerland. Infection 2020; 48 (04) 607-618
    CrossrefPubMedGoogle Scholar
  • 15 Kamonrattana R, Sathitsamitphong L, Choeyprasert W, Charoenkwan P, Natesirinilkul R, Fanhchaksai K. A randomized, open-labeled, prospective controlled study to assess the efficacy of frontline empirical intravenous piperacillin/tazobactam monotherapy in comparison with ceftazidime plus amikacin for febrile neutropenia in pediatric oncology patients. Asian Pac J Cancer Prev 2019; 20 (09) 2733-2737
    CrossrefPubMedGoogle Scholar
  • 16 Robinson PD, Lehrnbecher T, Phillips R, Dupuis LL, Sung L. Strategies for empiric management of pediatric fever and neutropenia in patients with cancer and hematopoietic stem-cell transplantation recipients: a systematic review of randomized trials. J Clin Oncol 2016; 34 (17) 2054-2060
    CrossrefPubMedGoogle Scholar
  • 17 Maxwell RR, Egan-Sherry D, Gill JB, Roth ME. Management of chemotherapy-induced febrile neutropenia in pediatric oncology patients: a North American survey of pediatric hematology/oncology and pediatric infectious disease physicians. Pediatr Blood Cancer 2017; 64 (12) e26700
    CrossrefPubMedGoogle Scholar
  • 18 Paolino J, Mariani J, Lucas A. et al. Outcomes of a clinical pathway for primary outpatient management of pediatric patients with low-risk febrile neutropenia. Pediatr Blood Cancer 2019; 66 (07) e27679
    CrossrefPubMedGoogle Scholar
  • 19 Orme LM, Babl FE, Barnes C, Barnett P, Donath S, Ashley DM. Outpatient versus inpatient IV antibiotic management for pediatric oncology patients with low risk febrile neutropenia: a randomised trial. Pediatr Blood Cancer 2014; 61 (08) 1427-1433
    CrossrefPubMedGoogle Scholar
  • 20 Avilés-Robles MJ, Reyes-López A, Otero-Mendoza FJ. et al. Safety and efficacy of step-down to oral outpatient treatment versus inpatient antimicrobial treatment in pediatric cancer patients with febrile neutropenia: a noninferiority multicenter randomized clinical trial. Pediatr Blood Cancer 2020; 67 (06) e28251
    CrossrefPubMedGoogle Scholar
  • 21 Taplitz RA, Kennedy EB, Bow EJ. et al. Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol 2018; 36 (14) 1443-1453
    CrossrefPubMedGoogle Scholar
  • 22 Phillips B, Selwood K, Lane SM, Skinner R, Gibson F, Chisholm JC. United Kingdom Children's Cancer Study Group. Variation in policies for the management of febrile neutropenia in United Kingdom Children's Cancer Study Group centres. Arch Dis Child 2007; 92 (06) 495-498
    CrossrefPubMedGoogle Scholar
  • 23 Das A, Trehan A, Bansal D. Risk factors for microbiologically-documented infections, mortality and prolonged hospital stay in children with febrile neutropenia. Indian Pediatr 2018; 55 (10) 859-864
    CrossrefPubMedGoogle Scholar
  • 24 Noronha V, Joshi A, Patil VM. et al. Pattern of infection, therapy, outcome and risk stratification of patients with febrile neutropenia in a tertiary care oncology hospital in India. Indian J Cancer 2014; 51 (04) 470-474
    CrossrefPubMedGoogle Scholar
  • 25 Radhakrishnan V, Vijaykumar V, Ganesan P, Rajendranath R, Trivadi G, Tenali S. Bloodstream infections in pediatric patients at Cancer Institute, Chennai. Indian J Cancer 2014; 51 (04) 418-419
    CrossrefPubMedGoogle Scholar
  • 26 Ten Berg S, Loeffen EAH, van de Wetering MD. et al. Development of pediatric oncology supportive care indicators: evaluation of febrile neutropenia care in the north of the Netherlands. Pediatr Blood Cancer 2019; 66 (02) e27504
    CrossrefPubMedGoogle Scholar
  • 27 Inaba H, Pei D, Wolf J. et al. Infection-related complications during treatment for childhood acute lymphoblastic leukemia. Ann Oncol 2017; 28 (02) 386-392
    CrossrefPubMedGoogle Scholar
  • 28 O'Connor D, Bate J, Wade R. et al. Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003. Blood 2014; 124 (07) 1056-1061
    CrossrefPubMedGoogle Scholar
  • 29 Basu SK, Fernandez ID, Fisher SG, Asselin BL, Lyman GH. Length of stay and mortality associated with febrile neutropenia among children with cancer. J Clin Oncol 2005; 23 (31) 7958-7966
    CrossrefPubMedGoogle Scholar
  • 30 Fletcher M, Hodgkiss H, Zhang S. et al. Prompt administration of antibiotics is associated with improved outcomes in febrile neutropenia in children with cancer. Pediatr Blood Cancer 2013; 60 (08) 1299-1306
    CrossrefPubMedGoogle Scholar
  • 31 Christensen MS, Heyman M, Möttönen M, Zeller B, Jonmundsson G, Hasle H. Nordic Society of Paediatric Haematology and Oncology (NOPHO). Treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992-2001. Br J Haematol 2005; 131 (01) 50-58
    CrossrefPubMedGoogle Scholar