Editor’s Note: Febrile neutropenia is a significant concern among immunocompromised patients due to the high infection-related mortality if left untreated. At the recent 4th Shanghai Symposium on Clinical Application of Autologous Hematopoietic Stem Cell Transplantation, Dr. Jie Xu of Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, discussed new empirical treatment approaches. This article consolidates the key points from her presentation.

Current Treatment Landscape and Challenges in Febrile Neutropenia

Over 80% of patients with hematologic malignancies develop febrile neutropenia following chemotherapy, with high mortality rates associated with bloodstream infections (BSI). Studies have shown that common sites of infection include the lungs, upper respiratory tract, perianal tissue, and bloodstream, highlighting the urgent need for effective empirical treatment due to the limited availability of microbiological evidence in many cases.

A multicenter prospective observational study involving 11 hematology centers across China found that among 784 febrile neutropenia cases, 32.3% were of unknown origin, 54.7% were clinically confirmed infections, and 13.0% were microbiologically confirmed infections .

Individualized Risk Assessment in Initial Empirical Therapy

Early empirical treatment is crucial for febrile neutropenic patients. Individualized assessments should consider risk stratification, drug resistance factors, local pathogen epidemiology, and patient complexity. High-risk patients require hospitalization, while low-risk criteria help identify patients suitable for outpatient care. Key drug resistance risk factors include prior exposure to broad-spectrum antibiotics, previous colonization with resistant pathogens, and prolonged hospital stays.

Rising resistance in gram-negative bacteria significantly correlates with increased mortality in febrile neutropenic patients . Data from China in 2022 indicate that Enterobacteriaceae, primarily carbapenem-resistant strains, are common in febrile neutropenic patients, and resistant strains present unique treatment challenges .

New Antimicrobial Therapies Offering Advanced Treatment Options

Among the innovative antibiotics, eravacycline (the first in the fluorocycline class) provides potent activity against multi-drug-resistant (MDR) gram-positive and gram-negative bacteria. Global data indicate that eravacycline outperforms tigecycline in effectiveness against carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae . Additionally, eravacycline shows strong efficacy against atypical pathogens, including Mycoplasma pneumoniae, making it a versatile option in complex infections.

In studies targeting CRE and CRAB, eravacycline demonstrated favorable outcomes when combined with other drugs like imipenem for CRAB and polymyxin B for CRE, achieving significant synergy in a range of difficult-to-treat infections .

Real-world studies have validated the effectiveness of eravacycline, showing clinical success rates as high as 94%, with minimal adverse effects primarily limited to nausea . In a multicenter retrospective study from the U.S., eravacycline achieved a 75.7% clinical success rate and a 94.7% 30-day survival rate among patients with MDR infections .

Given these results, eravacycline is now recommended in the 2022 ESCMID guidelines as an effective empirical therapy option for MDR gram-negative infections, underscoring its potential as a valuable new weapon against resistant infections

References

1. 中国中性粒细胞缺乏伴发热患者抗菌药物临床应用指南（2020年版）. 中华血液学杂志. 2020;41(12):969-978.
2. 闫晨华, 等. 中华血液学杂志. 2016, 37(3): 177-182.
3. Kara Ali R, et al. Ann Hematol. 2020 Aug;99(8):1925-1932.
4. 朱骏, 等. 中华血液学杂志, 2017, 38(11): 945-950.
5. Zhang Y, et al. Infect Drug Resist. 2020 Mar 26;13:903-910.
6. http://chinets.com/Data/GermYear
7. Logan LK, et al. J Infect Dis. 2017 Feb 15;215(suppl_1)
8. Chang H, et al. J Infect Public Health. 2020 May;13(5):784-790.
9. CHINET 2023年细菌耐药监测结果.
10. 中国碳青霉烯耐药肠杆菌科细菌感染诊治与防控专家共识[J]. 中华医学杂志, 2021, 101(36): 2850-2860.
11. 广泛耐药革兰阴性菌感染的实验诊断、抗菌治疗及医院感染控制:中国专家共识[J]. 中国感染与化疗杂志, 2017, 17(1): 82-93.
12. Hawser S, et al. J Glob Antimicrob Resis. 2023 Jun;33:304-320.
13. Microbiol Immunol Infect. 2023 Apr;56(2):358-366.
14. J Microbiol Immunol Infect. 2022 Oct;55(5):888-895.
15. Waites KB, et al. Antimicrob Agents Chemother. 2020 Jul 22;64(8)

.

1. J Glob Antimicrob Resist. 2022 Sep;30:56-59.
2. Bhavnani SM, Rubino CM, Hammel JP, et al. Pharmacokinetic-Pharmacodynamic (PK-PD) and Dose Selection Analyses for Eravacycline Using Phase 2 Data from Patients with Community-Acquired Complicated Intra-Abdominal Infections (cIAI).
3. Antimicrob Agents Chemother. 2014;58(4):1847-54.
4. Van Hise N, et al. Infect Dis Ther. 2020;9(4):1017-1028.
5. Alosaimy S, et al. Real-world Multi-center experience with ERV for complicated infection. ID WEEK 2020, Post.
6. Kunz Coyne AJ, et al. Microbiol Spectr. Published online November 29, 2023.
7. Clin Microbiol Infect. 2022 Apr;28(4):521-547.
8. Infectious Diseases Society of America antimicrobial resistant treatment guidance: gram-negative bacterial infections.

About Dr. Jie Xu

Dr. Jie Xu serves as the Director of the Infectious Diseases Department at Shanghai Ninth People’s Hospital and is a prominent voice in infection control and infectious disease research. She has held research fellowships in Israel and the U.S., contributing extensively to the molecular immunology of infectious diseases.