Skip to main content Accessibility help

Reducing Second Gram-Negative Antibiotic Therapy on Pediatric Oncology and Hematopoietic Stem Cell Transplantation Services

  • Rachel L. Wattier (a1), Emily R. Levy (a2), Amit J. Sabnis (a3), Christopher C. Dvorak (a4) and Andrew D. Auerbach (a5)...



To evaluate interventions to reduce avoidable antibiotic use on pediatric oncology and hematopoietic stem cell transplantation (HSCT) services.


Interrupted time series.


Academic pediatric hospital with separate oncology and HSCT services.


Children admitted to the services during baseline (October 2011–August 2013) and 2 intervention periods, September 2013–June 2015 and July 2015–June 2016, including 1,525 oncology hospitalizations and 301 HSCT hospitalizations.


In phase 1, we completed an update of the institutional febrile neutropenia (FN) guideline for the pediatric oncology service, recommending first-line β-lactam monotherapy rather than routine use of 2 gram-negative agents. Phase 2 included updating the HSCT service FN guideline and engagement with a new pediatric antimicrobial stewardship program. The use of target antibiotics (tobramycin and ciprofloxacin) was measured in days of therapy per 1,000 patient days collected from administrative data. Intervention effects were evaluated using interrupted time series with segmented regression.


Phase 1 had mixed effects–long-term reduction in tobramycin use (97% below projected at 18 months) but rebound with increasing slope in ciprofloxacin use (+18% per month). Following phase 2, tobramycin and ciprofloxacin use on the oncology service were both 99% below projected levels at 12 months. On the HSCT service, tobramycin use was 99% below the projected level and ciprofloxacin use was 96% below the projected level at 12 months.


Locally adapted guidelines can facilitate practice changes in oncology and HSCT settings. More comprehensive and ongoing interventions, including follow-up education, feedback, and engagement of companion services may be needed to sustain changes.

Infect Control Hosp Epidemiol 2017;38:1039–1047


Corresponding author

Address correspondence to Rachel L. Wattier, MD, MHS, 550 16th St 4th Floor Box 0434, San Francisco, CA, 94143-0434 (


Hide All

PREVIOUS PRESENTATION. This work was presented in part as a poster at the 7th Annual Pediatric Antimicrobial Stewardship Conference in Kansas City, Missouri, on June 3, 2016, and at the UCSF Health Improvement Symposium in San Francisco, California, on September 22, 2016.



Hide All
1. Caggiano, V, Weiss, RV, Rickert, TS, Linde-Zwirble, WT. Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer 2005;103:19161924.
2. Freifeld, AG, Bow, EJ, Sepkowitz, KA, et al. 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:e56e93.
3. Lehrnbecher, T, Phillips, R, Alexander, S, et al. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol 2012;30:44274438.
4. Averbuch, D, Orasch, C, Cordonnier, C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 2013;98:1826–1835.
5. Gyssens, IC, Kern, WV, Livermore, DM. The role of antibiotic stewardship in limiting antibacterial resistance among hematology patients. Haematologica 2013;98:18211825.
6. Taur, Y, Jenq, RR, Perales, M, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. 2014;124:1174–1182.
7. Wolf, J, Sun, Y, Tang, L, et al. Antimicrobial stewardship barriers and goals in pediatric oncology and bone marrow transplantation: a survey of antimicrobial stewardship practitioners. Infect Control Hosp Epidemiol 2016;37:343347.
8. Seo, SK, Lo, K, Abbo, LM. Current state of antimicrobial stewardship at solid organ and hematopoietic cell transplant centers in the United States. Infect Control Hosp Epidemiol 2016;37:11951200.
9. Barlam, TF, Cosgrove, SE, Abbo, LM, et al. Executive summary: implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62:11971202.
10. Nucci, M, Landau, M, Silveira, F, Spector, N, Pulcheri, W. Application of the IDSA guidelines for the use of antimicrobial agents in neutropenic patients: impact on reducing the use of glycopeptides. Infect Control Hosp Epidemiol 2001;22:651653.
11. Liew, YX, Lee, W, Cai, YY, et al. Utility and safety of procalcitonin in an antimicrobial stewardship program (ASP) in patients with malignancies. Eur J Clin Microbiol Infect Dis 2012;31:30413046.
12. Yeo, CL, Chan, DSG, Earnest, A, et al. Prospective audit and feedback on antibiotic prescription in an adult hematology-oncology unit in Singapore. Eur J Clin Microbiol Infect Dis 2012;31:583590.
13. Vicente, M, Al Nahedh, M, Parsad, S, Knoebel, RW, Pisano, J, Pettit, NN. Impact of a clinical pathway on appropriate empiric vancomycin use in cancer patients with febrile neutropenia. J Oncol Pharm Pract 2016. doi: 10.1177/1078155216668672.
14. 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;2:231242.
15. Paul, M, Soares-Weiser, K, Leibovici, L. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis. BMJ 2003;326:1111.
16. Wagner, AK, Soumerai, SB, Zhang, F, Ross-Degnan, D. Segmented regression analysis of interrupted time series studies in medication use research. J Clin Pharm Ther 2002;27:299309.
17. Alexander, SW, Wade, KC, Hibberd, PL, Parsons, SK. Evaluation of risk prediction criteria for episodes of febrile neutropenia in children with cancer. J Pediatr Hematol 2002;24:3842.
18. MacDougall, C, Polk, RE. Variability in rates of use of antibacterials among 130 US hospitals and risk-adjustment models for interhospital comparison. Infect Control Hosp Epidemiol 2008;29:203211.
19. Bartholomew, F, Aftandilian, C, Andrews, J, et al. Prescriber perceptions of a pediatric antimicrobial stewardship program. Clin Infect Dis 2015;53:18.
20. Grimshaw, JM, Russell, IT. Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet 1993;342:13171322.
21. Prior, M, Guerin, M, Grimmer-Somers, K. The effectiveness of clinical guideline implementation strategies—a synthesis of systematic review findings. J Eval Clin Pract 2008;14:888897.
22. Forsner, T, Wistedt, AA, Brommels, M, Janszky, I, de Leon, AP, Forsell, Y. Supported local implementation of clinical guidelines in psychiatry: a two-year follow-up. Implement Sci 2010;5:4.
23. Schnoor, M, Meyer, T, Suttorp, N, Raspe, H, Welte, T, Schäfer, T. Development and evaluation of an implementation strategy for the German guideline on community-acquired pneumonia. Qual Saf Health Care 2010;19:498502.
24. Storm-Versloot, MN, Knops, AM, Ubbink, DT, Goossens, A, Legemate, DA, Vermeulen, H. Long-term adherence to a local guideline on postoperative body temperature measurement: mixed methods analysis. J Eval Clin Pract 2012;18:841847.
25. Pakyz, AL, Moczygemba, LR, Vanderwielen, LM, Edmond, MB, Stevens, MP, Kuzel, AJ. Facilitators and barriers to implementing antimicrobial stewardship strategies: Results from a qualitative study. Am J Infect Control 2014;42:S257S263.
26. Jeffs, L, Thampi, N, Maione, M, Steinberg, M, Morris, AM, Bell, CM. A qualitative analysis of implementation of antimicrobial stewardship at 3 academic hospitals: understanding the key influences on success. Can J Hosp Pharm 2015;68:395400.
27. Tunis, SR, Hayward, RS, Wilson, MC, et al. Internists’ attitudes about clinical practice guidelines. Ann Intern Med 1994;120:956963.


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed