1
• Implementation of a risk-stratification guideline for the treatment of NF resulted in decreased meropenem utilization without negatively impacting patient outcomes • Appropriate use of the NF guideline would have resulted in appropriate empiric anti-pseudomonal antimicrobial therapy in all patients − Further education on utilization of the NF guideline is needed to promote guideline compliance • Despite an overall decrease in carbapenem use, use of the NF guideline still results in a significant number of patients without cefepime-resistant infections qualifying to receive meropenem, suggesting that further tailoring of this guideline is still possible *multidrug-resistant: resistance to multiple classes of antibiotics, specifically anti-pseudomonal beta-lactams • Approximately 10-50% of patients with solid tumors and >80% of patients with hematologic malignancies develop neutropenic fever (NF) at least once during each chemotherapy cycle 1 • Empiric anti-pseudomonal antimicrobials are the recommended agent of choice for treatment of NF, due to high mortality associated with Pseudomonas aeruginosa 1 • The Infectious Diseases Society of America (IDSA) does not make specific recommendations regarding choice of anti- pseudomonal agent 1 − Choices include carbapenems (meropenem, imipenem- cilastatin, doripenem), cefepime, piperacillin-tazobactam • No differences in clinical outcomes between the anti- pseudomonal agents have been identified, thus broader spectrum anti-pseudomonals (such as carbapenems) may not be necessary for all patients with NF 2-4 − Due to increasing rates of resistance driven by overuse of antimicrobials, it is prudent to reserve carbapenems if possible for high-risk populations Evaluation of a Risk Stratification Guideline for the Treatment of Neutropenic Fever for Oncology Patients Amber Wollenziehn, PharmD; Aaron Lorge, PharmD, BCOP; Sara Revolinski, PharmD, BCPS; Angela Huang, PharmD, BCPS AQ-ID Froedtert & the Medical College of Wisconsin | Froedtert Hospital | Milwaukee, WI • The purpose of this study is to evaluate the use of a risk stratification tool to determine empiric anti-pseudomonal agent for NF • Single-center retrospective review of NF patients pre- and post-implementation of a NF guideline at Froedtert Hospital − Pre-implementation: Jan 1, 2015 - June 30, 2015 − Guideline implemented: − Post-implementation: June 23, 2016 - Dec 31, 2016 • Inclusion criteria: patients ≥18 yo with an underlying malignancy and NF and received an empiric anti- pseudomonal agent for treatment of NF − Neutropenic fever definition 1 : white blood cell (WBC) <500cells/mm 3 and a single temperature ≥38.3⁰F (101⁰F) or a temperature of ≥38⁰F (100.4⁰F) for ≥1 hour • Primary outcome: incidence of inappropriate empiric anti- pseudomonal antimicrobial therapy, as defined by isolation of a gram-negative organism resistant to the recommended anti-pseudomonal agent based on institutional NF guidelines • Secondary outcomes: − 30-day all-cause mortality − Percentage of patients receiving meropenem pre- versus post-guideline implementation − NF guideline concordance, defined as appropriate empiric anti-pseudomonal agent chosen based on institution’s risk stratification guideline Disclosure: Authors of this presentation have nothing to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation 1. Freifeld A, Bow E, Sepkowitz K, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 updated by the Infectious Disease Society of America. Clin Infect Dis. 2011 Feb 15;52(4):427-431. 2. Marini BL, Hough SM, Gregg KS, Abu-seir H, Nagel JL. Risk factors for piperacillin/tazobactam-resistant Gram-negative infection in hematology/oncology patients with febrile neutropenia. Support Care Cancer. 2015;23(8):2287-2295. 3. Bow E, Rotstein C, Moskin G, et al. 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):447-459. 4. Nakane T, Tamura K, Hino M, et al. Cefozopran, meropenem, or imipenem-cilastin compared with cefepime as empirical therapy in febrile neutropenic adult patients: a multicenter prospective randomized trial. J Infect Chemother. 2015 Jan;21(1):16-22. Secondary Outcomes • Pre-intervention Group: 26/79 (32.8%) of patients would have met criteria to receive meropenem but 71/79 (89.9%) of patients received it • Post-intervention Group: 29/91 (41.8%) of patients met criteria to receive meropenem and 8/91 (8.8%) received it − This was due to primary-teams opting to use non-carbapenems despite meeting criteria for use Background Methods Neutropenic Fever Treatment Algorithm Results Conclusions References Table 1: Baseline Demographics Primary Outcome • In the post-guideline group, 29 gram-negative organisms were identified, of which 4 were resistant to cefepime (Figure 1) − Because Stenotrophomonas maltophilia is not covered by most anti-pseudomonal agents and empiric coverage of this organism in NF is not common, this isolate was not included the primary outcome analysis, but is included in Figure 1 − The remaining 3 cefepime-resistant organisms were meropenem susceptible − All 3 patients met criteria to receive meropenem, thus incidence of inappropriate anti-pseudomonal antimicrobial therapy based on guideline-criteria was 0%. o Due to guideline non-compliance, 2/3 of these patients did not receive meropenem Pre-Group (n=79) Post-Group (n=91) P-value Age (years) (med, IQR) 61 (51-66) 60 (48.5-67) 0.45 Female (no.,%) 45 (57.0) 72 (79.1) 0.75 Weight (kg) (med, IQR) 81.9 (70.3-99.1) 83.4 (71.8-97.4) 0.45 Service Bone Marrow Transplant (no., %) 38 (48.1) 37 (40.7) 0.36 Hematologic Malignancy (no., %) 32 (40.5) 44 (48.4) 0.35 Solid Tumor Oncology (no., %) 9 (11.4) 10 (11.0) 1.0 Allogeneic bone marrow transplant (no., %) 19 (24.1) 19 (20.9) 1.0 Duration of last chemotherapy regimen (days) (med, IQR) 5.5 (0-5) 4.0 (0-5) 0.14 Pre-Group (n=79) Post-Group (n=91) P-value 30-day all-cause mortality (no., %) 14 (17.7) 14 (15.4) 0.69 Meropenem utilization (no., %) 71 (89.9) 8 (8.8) <0.001 NF guideline concordance (no., %) 30 (38.0) 70 (76.9) <0.001 Results Correspondence: Angela Huang, PharmD, BCPS AQ-ID Froedtert Hospital 9200 W. Wisconsin Ave Milwaukee, WI 53226 [email protected] 1577 Hematology/Oncology patient presents with fever and neutropenia H&P: help determine potential source of infection - review prior cultures; ensure empiric antimicrobials adequately cover previous infections Cultures: obtain 2-3 sets of blood cultures: 1 set peripheral + 1 set central venous catheter (preferred) or 2 set peripheral blood culture Labs: obtain CBC + diff, CMP, urinalysis + culture and sensitivity, +lactate if concern for sepsis/septic shock Imaging: chest X-ray if signs/symptoms of respiratory involvement, CT abdomen/pelvis if potential abdominal source Does the patient meet any of the following? Broad spectrum antibiotic use for >14 days (cumulative) in the past 90 days History of multidrug resistant* gram-negative rod bacteria from any site Sepsis, defined as 2 or more of the following: altered mental status, RR ≥ 22, SBP ≤ 100 History of life-threatening allergy to penicillins Yes No Cefepime 2g IV Q8h extended-infusion (EI) For aspiration, intra-abdominal infective source, non-life threatening cephalosporin: Piperacillin/tazobactam 4.5g IV Q8h EI Meropenem 1g IV Q8h EI Alternative for penicillin allergy: Aztreonam 2g IV Q8h ± tobramycin (pharmacy to dose) 0 1 2 3 4 5 6 7 8 9 E. coli Klebsiella oxytoca Klebisella pneumoniae Pseudomonas spp. Enterobacter cloacae Citrobacter freundii S. maltophilia Leclercia adecarboxylata Unspecified GNRs in urine Number of Isolates Organisms Figure 1: Gram-negative Organisms Isolated from the Post-Intervention Group Resistant to Anti-pseudomonals* Cefepime Susceptible Cefepime Resistant/Meropenem Susceptible *Some S. maltophilia may be susceptible to ceftazidime, however this anti-pseudomonal agent is not commonly used for NF due to limited gram-positive coverage
